PeproTech Inc.
Originally published online as doi:10.1189/jlb.0306154 on August 17, 2006

Published online before print August 17, 2006
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jlb.0306154v1
80/5/984    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hosmalin, A.
Right arrow Articles by Lebon, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hosmalin, A.
Right arrow Articles by Lebon, P.
(Journal of Leukocyte Biology. 2006;80:984-993.)
© 2006 by Society for Leukocyte Biology

Type I interferon production in HIV-infected patients

Anne Hosmalin*,{dagger},{ddagger},§,1 and Pierre Lebon§

* Institut Cochin, Département d'Immunologie, Paris, F-75014, France;
{dagger} INSERM U567, Paris, F-75014, France;
{ddagger} CNRS, UMR-S 8104, Paris, F-75014, France; and
§ Université Paris 5, Faculté de Médecine René Descartes, UM3, Paris, F-75014, France

1 Correspondence: Institut Cochin, Département d'Immunologie, 27, rue du Fg St. Jacques, Bat Gustave Roussy 8eme etage, Paris 75014, France. E-mail: hosmalin{at}cochin.inserm.fr


arrow
ABSTRACT
 
Type I IFNs display multiple biological effects. They have a strong antiviral action, not only directly but also indirectly through activation of the immune system. They may also have actions that are deleterious for the host. The cells that produce type I IFN are mostly plasmacytoid dendritic cells (pDC), but this depends on the viral stimulus. The migration and distribution of pDC into lymphoid organs, driven by chemokine interactions with their ligands, determines interaction with different cell types. In HIV infection, IFN production in vitro is impaired during primary infection and later in association with opportunistic infections. Circulating pDC numbers are decreased in parallel. These parameters may be used to help assess the prognosis of the disease and to monitor treatment.

Key Words: plasmacytoid dendritic cells • innate immunity • adaptive immunity • immune therapy • vaccination • primary infection • virus


arrow
INTRODUCTION
 
IFN can protect from viral infection [1 ]. Human type I IFNs comprise 13 subtypes of IFN-{alpha}, in addition to IFN-ß, -{omega}, -{delta}, -{tau}, and -{kappa}. These different IFNs share the same IFN-{alpha}/-ß receptor. IFN-like molecules or type III IFNs with similar properties also include limitin (mouse), IL-28A or IFN-lambda2, IL-28B or IFN-lambda3, and IL-29 or IFN-lambda1; they share a distinct class II cytokine receptor [2 3 4 5 6 ].


arrow
ANTIVIRAL ROLE OF TYPE I IFN
 
Antiviral role of type I IFN in vivo
The antiviral role of type I IFN was shown in vivo: anti-interferon sera administration increased dramatically the susceptibility to acute challenges with lymphocytic choriomeningitis, encephalomyocarditis, herpes simplex, maloney sarcoma, vesicular stomatitis, Newcastle disease, and influenza viruses. Mice impaired for the IFN-{alpha}/-ß receptor were extremely susceptible to acute challenges with vesicular stomatitis, Semliki Forest, vaccinia, or the noncytopathic lymphocytic choriomeningitis WE strain viruses [7 8 9 10 ]. IFN-{alpha} is currently widely used to treat viral hepatitis B and C [11 ]. A transitory peak of type I IFN was found in the plasma of SIV-infected macaques around day 10 postinfection, concomitant to the peak of plasma viral load [12 ]. In draining lymph nodes from rhesus macaques infected intravaginally by SIV mac-251 or -239, elevated IFN-{alpha} mRNA levels susceptible to have an antiviral activity were found too late to prevent viral replication and dissemination, whereas pro-inflammatory cytokine mRNA susceptible to recruit potential targets for SIV were found earlier [13 , 14 ].When patients were studied during primary HIV infection, on average 2 months postinfection, type I IFN was not detectable in the plasma, at least by conventional methods in our hands [15 ].

The capacity of natural interferon producing cells (NIPC) within PBMC to produce IFN-{alpha} in vitro in response to stimulation by HSV-1 or other viral stimulation is impaired during chronic HIV infection in association with occurrence of opportunistic infections and Kaposi sarcoma [16 17 18 19 20 21 22 23 ]. Conversely, IFN-{alpha} production is higher in asymptomatic long-term survivors than in uninfected controls [24 ]. It is dramatically impaired during primary infection [15 ], adding another subclinical tendency toward immune deficiency to those that are already known during this stage, like low CD4 T cell counts [25 ]. This impairment was less pronounced after a follow-up of 1 year in untreated patients, but it was corrected in highly active antiretroviral therapy (HAART) treated patients [15 ]. This effect of HAART needs to be assessed in a larger cohort of patients. Primary infection is the stage in which a balance is set between viral replication and immune responses, depending on viral strain characteristics and host genetic factors [26 ]. The future evolution of these patients will tell whether the loss of IFN production in vitro during this stage is detrimental for the outcome of the disease. In chronically infected, progressive patients, reconstitution of IFN-{alpha} production, associated with protection from recurrent or opportunistic infection, was obtained by HAART [27 ]. Interestingly, this restoration occurred earlier than that of CD4 T cell counts [28 ]. Overall, a correlation seems to appear between high IFN-{alpha} production capacities and low HIV viral loads and high CD4 cell counts and lack of opportunistic infections [24 , 27 , 29 ]. These correlations can be related to the direct antiviral role of IFN-{alpha} or -ß on HIV-1 infected cells in different models using severe combined immunodeficient mice [30 31 32 33 ].

Type I IFN activation and mechanisms of action
HIV-1 stimulates plasmacytoid dendritic cells (pDC) through TLR7 [34 ] and apparently CD4 [35 ]. Induction of type I IFN by viruses can also be mediated through binding of viral RNA or DNA to TLR3, -8, or -9. Induction of type I IFN through TLR7, -8, and -9 is mediated by the adaptor molecule myeloid differentiation primary response protein 88 (MyD88), interferon regulatory factor (IRF)-7 and finally NF-{kappa}B activation. Induction of type I IFN by viruses can also be mediated through TLR-independent pathways, involving cytoplasmic sensors, like the retinoic acid-inducible gene I (RIG-I) and the melanoma differentiation-associated gene 5 (MDA5). This leads to IRF3 activation and finally NF-{kappa}B activation [36 ].

Type I IFNs induce or enhance the expression of many genes [37 ] through a cell transmembrane receptor composed of two subunits, IFNAR1 and IFNAR2. Binding of the receptors leads to a cascade of phosphorylation of kinases, JAK1 and Tyk2, and subsequently to the tyrosine phosphorylation of signal transducers and activators of STAT1 and STAT2. These activated STAT form a complex with IRF9, ISGF3, which translocates to the nucleus and binds to DNA sequences of IFN-stimulated genes (ISG) containing IFN-stimulated response elements (ISRE). More than 100 ISG are transcribed, and their products are involved in the different properties of interferons such as antiviral, antiproliferative, apoptosis, and immunomodulatory properties. The main ISG encode for the protein kinase stimulated by ds RNA (PKR), the 2’-5'oligoadenylate synthetases (OAS), and the myxovirus resistance GTPase (MX), but also the ISG 20. PKR is a serine threonine kinase, which, in the presence of dsRNA, phosphorylates substrates, among which the subunit {alpha} of the eukaryotic initiation factor 2-{alpha} (eIF2{alpha}) stops protein translation. OAS, in the presence of dsRNA, synthesizes 2'5' oligoadenylates, which activate endogenous cytoplasmic RNase L (RNase L) and lead to the degradation of viral and cellular mRNA. PKR and OAS are also involved in cellular apoptosis. MxA, from the dynamin family, inhibits the RNA polymerase of influenza viruses and more generally appears to detect viral infection by sensing nucleocapsid-like structures and trapping them into specific subcellular compartments to make them unavailable for the generation of new virus particles [36 , 38 ].

The antiviral activity of type I IFN can also be mediated by different actors of the immune system [3 , 36 ]. Indeed, type I interferons amplify their own expression through induction of IRF-7 [39 ] and through accumulation of plasmacytoid dendritic cells (pDC) [40 ]. They activate the lytic potential and proliferation of NK and {gamma}{delta} T cells and NO synthesis by macrophages. They also enhance lysis of infected cells by cytotoxic T cells or T helper type 1 cells, as well as IFN-{gamma} production by T lymphocytes [41 ]. During LCMV infection, the activation of CD8 T cells depends on their ability to respond to type I IFN [42 43 44 45 ]. Type I IFN increase class I MHC expression on all cell types, perhaps counteracting the effect of HIV Nef [46 , 47 ], and thus potentially increasing recognition and lysis by specific CD8+ T lymphocytes. In addition, cross-presentation by DC is enhanced through the action of virally-induced type I IFN [48 ], and this presentation pathway is probably crucial so as to enhance viral antigen presentation while avoiding autoimmune recognition [49 50 51 52 53 ]. Conversely, high levels of type I IFN inhibit IL-12 expression and IL-12 activation of NK cell IFN-{gamma} production [41 ]. STAT1 has a critical role in many of these effects [36 ].

Role of type I IFN on HIV replication in vitro
Type I IFNs inhibit the replication of HIV-1 [54 55 56 ], especially when cells are pretreated by IFN before infection; this effect acts on the integration and the reverse transcriptase activity of the virus [57 , 58 ]. When cells are treated by IFN after infection, the antiviral effect is less pronounced [57 , 59 ]. IFN is supposed to block the association of RNAs to polyribosomes and inhibit viral particle assembly through posttranslational modification of viral proteins. A weak but continuous production of IFN-ß by the PBMC of healthy donors or of HIV+ patients, after transduction by a retroviral vector encoding for IFN-ß, protects them from HIV-1 infection; blockade of viral infection using this mechanism seems to occur at a very early stage of HIV-1 replication [60 ]. HIV-1 induces directly the synthesis of the MxA gene [61 ] and of the 2-5A synthetase [62 ] but not of other interferon-inducible genes [61 ]. The direct induction of the 2-5A synthetase makes HIV-infected cells resistant to another viral infection, particularly vesicular stomatitis virus (VSV) infection and may play a role in the control of HIV protein synthesis. Indeed in vitro, HIV-1 production is strongly inhibited by transfection of the 2-5A synthetase gene [63 ]. 2’-5' Oligoadenylates and analogs can inhibit the reverse transcriptase activity of HIV-1 [62 ].

Viral escape to the effects of type I IFN
Viruses have the genetic capacity to downmodulate IFN production or inhibit responses to IFN [36 , 64 ]. Inhibition of IFN induction in infected cells occurs through viral proteins that block the activation of IRF-3 after interaction with ds RNA, preventing the activation through TLR3 or TLR-independent sensors such as RIG-I and MDA 5 [36 , 64 ]. Some strains of RSV and measles inhibit IFN production by pDCs, although the molecular mechanisms involved are unknown [64 ]. Inhibition of the response of infected cells to IFN has recently been demonstrated in the case of cytomegaloviruses and involves specific targeting and degradation of STAT-2 [64 ]. No evident inhibition of IFN induction by HIV was reported. A sequence in the 5' HIV-1 long terminal repeat (LTR) contains a binding site for transcription factors of the IRF family. IRF-1 is produced early upon virus entry in CD4+ T cells and before expression of Tat. IRF-1 activates HIV-1 long terminal repeat (LTR) transcription and also cooperates with Tat in amplifying virus gene transcription and replication. IRF-1 is mostly expressed under the action of IFN-{gamma} in activated T cells and not under the action of type 1 IFN [65 ]. The HIV-1 transactivating response (TAR) RNA can activate the 2-5A synthetase and PKR [66 ]. However, HIV induces the expression of the RNase L inhibitor, which antagonizes the binding of 2’-5'A oligoadenylates to RNase L [67 ]. PKR can be activated by HIV through binding to the ds RNA region TAR of the LTR [68 ]. The transactivating protein Tat and the cellular TAR RNA binding protein (TRBP) also bind to TAR and to PKR and behave as inhibitors of the autophosphorylation of PKR during viral infection, therefore inhibiting its action on the eIF2{alpha} substrate and on protein synthesis. TRBP is part of a Dicer complex and is required for RNA interference; it is perhaps diverted by HIV-1 [69 70 71 ]. Moreover, PKR can phosphorylate HIV Tat and enhance its capacity to transactivate the LTR [72 ]. TAR and Tat, therefore, participate actively in viral escape to the effects of type I IFN.


arrow
ADVERSE ROLES OF TYPE I IFN IN VIRAL INFECTION
 
All the effector mechanisms of the immune system that reduce viral replication have mirroring adverse effects on the host. Type I and type II IFNs induce a cytotoxic activity in antigen presenting cells. HIV itself, like other viruses, induces a cytotoxic activity in monocytes [73 ], DC [74 ], and CD4 T cells themselves [35 ] against infected CD4 T lymphocytes but also against uninfected cells. TRAIL mediates at least in part the cytotoxicity of monocytes, in a type I IFN-dependent way [75 ]. In vitro, HIV-1 gp120 induces in CD4 T lymphocytes both sensitivity to TRAIL directly and TRAIL expression indirectly, through the stimulation of CD4, which induces type I IFN secretion by pDC [35 ]. These cytotoxic mechanisms, as well as those stimulated in NK cells [76 ] or bystander T cells, can be responsible for the high susceptibility to apoptosis of uninfected CD4 T cells that are found in HIV-infected patients [77 ]. Indeed, TRAIL neutralization in HIV-1 infected Hu-PBL-NOD-SCID mice inhibits human CD4 T cell apoptosis induced by HIV-1 infection [78 ]. Moreover, soluble TRAIL is found in the plasma of HIV-1 infected patients and is decreased by HAART in correlation with viral load [75 ]. In addition, in the SCID-hu Thy/liv mouse model and in thymus organ cultures, HIV-1 induces pDC to secrete type I IFN, which in turn up-regulates MHC class I molecule expression on most thymocytes [79 ]. This may lead to thymic selection of dysfunctional CD8+ T lymphocytes [80 ].

Early work has suggested a deleterious effect of high concentrations of IFN-{alpha} (i.e., inhibition of T cell proliferation, inhibition of chemokine production) and even proposed immunization against this cytokine as a therapeutic approach against AIDS [81 , 82 ]. A dichotomy may exist between positive and negative effects of IFN-{alpha} in the early vs. late stages of the disease. IFN-{alpha} has been shown to be potentially beneficial on HIV viral loads during early stages of infection, but not later [83 ]. In chronic lymphocytic choriomeningitis virus (LCMV) infection, administration of anti-IFN serum inhibits pathogenesis [84 ]. During acute LCMV infection in mice, while type I IFN activate effector CD8 T cell responses, they also prevent renewal of the DCs [85 ] and drive the early attrition of CD8 T cells [86 , 87 ]. Besides their effects in viral infections, type I IFN can enhance autoimmunity; particularly, the high levels of type I IFN found in the sera of systemic lupus erythematosus induce differentiation of monocytes into DC and probably exacerbate the pathogenesis of the disease [88 , 89 ]. How the outcome of the balance between negative and positive effects of IFN on antiviral immune responses is regulated needs further investigation but it may depend on the kinetics, levels and anatomical location of IFN release.


arrow
PLASMACYTOID DENDRITIC CELLS AND OTHER CELL TYPES RESPONSIBLE FOR TYPE I IFN PRODUCTION
 
The major human peripheral blood mononuclear cell subset that was responsible for the production in vitro of IFN-{alpha} in response to influenza, Sendai, and Newcastle disease viruses was first identified as an HLA-DR+, DC-related population lacking the markers for other cell lineages [90 , 91 ]. This population was nonadherent and stimulated allogeneic T cell proliferation poorly [92 ]. NIPC or IPC were eventually identified as plasmacytoid dendritic cells (pDC) [93 94 95 96 97 98 99 100 101 102 103 ]. They are present in lymph nodes, tonsils, and blood with a very low frequency and they produce 100 times more type I IFN per cell than monocytes.When they are depleted in vivo, the response to mCMV infection or to CpG or oligoribonucleotide injection is abolished [103 104 105 106 ]. In some infections, like LCMV infection, pDC are not the major population responsible for the early IFN-{alpha} response [104 ]. In humans, pDC produce IFN-{alpha} [107 ] after stimulation by live or inactivated HIV [108 , 109 ]. IFN-{alpha} in turn sustains pDC survival [110 , 111 ].

pDC counts are reduced during chronic as well as primary HIV-1 infection [22 23 24 , 27 , 112 113 114 115 116 ]. A correlation with plasma viral load [24 , 27 , 112 ] and/or with peripheral CD4 T cell counts [112 , 114 , 115 , 117 ] was found in most, but not all, studies [22 , 114 ]. A correlation with lymphoproliferative responses against HIV-1 p24 was found in one study [114 ]. In a pediatric study, pDC counts were found to be lower in viremic children with a history of decreasing CD4 T cell percentages compared with children with stable CD4 T cell counts [115 ]. The pDC count defect is already found at the onset of primary infection. Strikingly, at the onset of primary HIV infection and not at later time points in HIV or HCV [118 ] infection, the correlation between pDC counts and type I IFN production is lost [15 ], indicating loss of function in some pDC.

Why are circulating pDC numbers reduced in HIV patients? A central bone marrow precursor defect may be involved, as for T lymphocyte precursors in macaques [119 , 120 ]. pDC may also be destroyed in the periphery by the virus itself. Indeed, HIV infects pDC in vitro with cytopathogenicity [108 , 121 , 122 ], and infected pDC are found in the tonsils, thymus, and blood from HIV-infected patients [123 , 124 ]. pDC may also strive less because of lower IFN production [29 ] or defective interaction with CD4 T lymphocytes [124 ]. In any case, pDC probably home to lymph nodes during HIV infection [125 126 127 ]. In the SIV infection model, many activated DC were found in lymphoid tissues in primary or asymptomatic infection, but at the stage of AIDS only few activated CD83+ DC were found in the lymph nodes [127 ]. This finding was consistent with the lower capacity to up-regulate CD83, a terminal differentiation molecule, on spleen DC from late-stage HIV-infected patients [128 ].

Thus, the mechanisms responsible for the loss of circulating DC are not identified but may reflect different mechanisms, including homing to the lymphoid organs. This homing may help induce antiviral responses on one hand and hyperactivation of the immune system on the other; whereas a lack of DC activation in the lymphoid organs may reflect the failure of the immune system in AIDS.


arrow
HOMING AND CELL INTERACTION
 
Compartmentalization is a key to understanding all biological responses, including immune responses. Type I IFN production will occur where the pDC are driven by viral stimulation, and relevant data must be sought not only in blood but also in lymphoid organs [129 130 131 ]. Migration of DC upon stimulation is selectively driven by the successive expression of different chemokine receptors and integrins [132 ]. Human pDC express L-selectin (CD62L), which probably drives their entry into the lymph nodes through high endothelial venules in the steady state, likewise to what has been demonstrated in mice [94 , 100 , 133 , 134 ]. During bacterial- or viral-driven inflammation, the expression of CXCR3 is required for pDC migration into the lymph nodes in a CXCL9- and E-selectin-dependent manner [135 ]. Plasmacytoid DC migration into inflamed tissues or tumors can also be mediated by CXCR4 and driven by SDF-1/CXCL12 [136 ]; by ChemR23, driven by chemerin [137 ]; and by CCR1, CCR2, and CCR5, receptors for inflammatory cytokines [102 ]. Once activated, pDC express CCR7, the receptor for the chemokines MIP3ß/CCL19 and SLC or 6Ckine/CCL212, which attract them into the T cell areas of secondary lymphoid organs [138 ]. In HIV infection, homing of pDC to the lymph nodes [125 ] would be consistent with the in vitro induction by HIV-1 of CCR7 expression and of migration toward CCL19 [139 ]. In mice, pDC differ from mDC in the in vivo response to TLR ligands, in terms of pattern and type I IFN requirement for activation and migration [140 ].

Human pDC have a successive chemokine expression pattern susceptible to attract other cell populations—first effector cells (cytotoxic T and NK cells and neutrophils), then effector memory T cells, then naive T and B lymphocytes—while they mature and putatively progress toward the T cell zones of the secondary lymphoid organs [141 142 143 144 ]. In addition, the cross-talk between mDC, pDC, monocytes, T and B lymphocytes, neutrophils, and NK cells in HIV infection needs to be explored [115 , 116 , 145 146 147 ]. The relations between pDC and the regulatory T cells that hinder antiviral effector responses as well as pathogenic hyperactivation of the immune system in HIV and SIV infections [148 149 150 151 152 153 154 ] will be interesting to study, because pDC can induce regulatory T cells [155 156 157 ]. Indeed, semi-mature pDC and mDC and FoxP3+CD4+ T cells were found in the lymph nodes from untreated HIV+ patients in higher proportions than in lymph nodes from treated HIV+ patients or from HIV patients [158 ].

CCR5- and CXCR4-using HIV-1 isolates stimulate pDC maturation (up-regulation of CD83, CCR7, costimulation molecules, migration toward CCL19) and secretion of TNF-{alpha} and IFN-{alpha} [108 , 139 , 159 ]. In contrast, in response mostly to CCR5-using HIV-1 isolates, depending on the laboratories and probably on the concentration used, mDC undergo at least partial maturation but do not secrete either type I IFN nor bioactive IL-12 p70 [159 , 160 ]. However, when pDC and mDC are co-cultured with HIV, IFN and TNF-{alpha} secretion by pDC induces mDC maturation [139 ]. Virus replication is enhanced after pDC treatment with CD40L and antibodies against IFN-{alpha}, probably because of the reduction in IFN-{alpha} production [122 , 123 ]. HIV-1 infection is transferred from pDC as well as from mDC, most efficiently toward antigen-specific CD4+ T cells [161 ].


arrow
PREDICTIVE FACTORS DURING HIV INFECTION
 
The results described above hint that pDC counts (when they will be standardized [15 ]) and/or in vitro type I IFN production might be used as predictive factors during HIV infection, as well as in other infections. Indeed, in dengue virus infection, children who developed hemorrhagic dengue fever had an early decrease in circulating pDC levels, which was not found in those who had more benign forms of the disease [162 ]. In tuberculosis, pDC count recovery correlates with successful antibiotic treatment [163 ]. Other predictive factors in HIV infection include: baseline levels of CD4 T cell counts and plasma HIV RNA; the nadir CD4 T cell count, as well as parameters such as CD4 T cell counts; proviral DNA load in peripheral blood mononuclear cells; anti-p24 lymphoproliferative response at the time of treatment interruption; and immunologic setpoint activation, as measured by median density of CD38 molecules on CD4 and CD8 T cells [164 165 166 167 168 169 ]. However, these factors are not completely predictive of disease progression in at least three circumstances.

The first circumstance is the decision to treat by HAART early during acute or primary infection. Here, the putative restoration of type I IFN production under HAART [15 ] adds an additional argument, together with the reduction of CD8 T cell oligoclonality [170 ] and the increase in specific CD4 responses [171 , 172 ], for the use of HAART to preserve the immune system while viral populations are homogeneous, thus preventing virus spreading. However, there is limited durability [173 ], early resistance induction [169 , 174 ], long-term drug-associated toxicity, and lack of adherence [26 ].

The second circumstance is to evaluate HAART success: a recovery in pDC counts, at least partial, or in type I IFN production, was obtained in several studies but not all [22 ], through HAART during chronic infection [27 , 117 ] and probably during primary infection [15 , 175 ]. This recovery sometimes correlated with a recovery in CD4 T cell counts and/or a decrease in viral load [27 , 113 , 117 ]. pDC count recovery was earlier and more pronounced than CD4 count recovery [28 , 117 ].

The third circumstance is the counseling of patients who request HAART interruption because of side effects. One study on patients with primary HIV-1 infection with undetectable viral loads under HAART showed that pDC count recovery during HAART correlated with the ability to control spontaneously replication after treatment interruption [175 ]. This pilot study needs further confirmation in large cohorts of chronically infected patients [167 ]. pDC counts, in addition to baseline viral load and other predictive factors, might help in counseling the patients on their risk of viral replication rebound.


arrow
Type I IFN administration or stimulation as therapy against HIV infection
 
IFN-{alpha} is currently being tested in clinical trials, particularly during primary HIV infection, where it might supplement defective production [15 ] and where promising results were obtained [176 ], as formerly in asymptomatic chronic infection [83 ]. Type I IFN production might also be stimulated by TLR ligands, if pDC can still respond. More interestingly, it might be stimulated by CpG or imiquimod analogs for antiviral protection at the mucosal level [177 178 179 180 ]. However, caution must be exercised to avoid hyperactivation of the mucosal immune system that would increase viral replication [181 ]. Finally, IFN-{alpha} is a strong adjuvant in vaccination [182 ]. It induces the differentiation of monocyte-derived DC for cell therapy [183 , 184 ]. CpG oligonucleotides can stimulate not only pDC, but also B cells [185 ], for systemic and mucosal vaccination; indeed they induce strong local T cell immune responses in the genital tract and cross-clade protection [186 , 187 ]. Therefore, type I IFN administration or stimulation may have strong potential in future immune therapies against HIV.


arrow
CONCLUSION
 
Correlative data indicate that type I IFN produced by pDC have a role in the control of HIV infection, although pathogenicity may also be induced [188 189 190 191 192 193 194 195 196 ]. The role of homing into lymphoid organs and of interactions with other cell types still needs intensive studying during this infection. Plasmacytoid DC counts and/or of type I IFN production tests in vitro might be used as predictive factors during HIV infection, to evaluate HAART success or to counsel patients who want to interrupt HAART about their risk of viral rebound. Immune therapy and vaccination can use either IFN-{alpha} itself or its induction by TLR ligands to obtain better viral replication control and stimulation of antigen-specific immune responses. The mechanisms of viral escape to the effects of type I IFN need to be understood further to lead to better targeted therapies.


arrow
ACKNOWLEDGEMENTS
 
The authors thank Michaela Müller-Trutwin (Pasteur Institute, Paris), Stéphanie Louis, Michelina Nascimbeni, Concepción Marañón, Miriam Lichtner, Sandrine Kahi, Leyla Develioglu, Isabelle Kamga, Aurélie Teissonnière, Ludovic Fery, Laurent Chorro, Seckou Diocou, Guillaume Hoeffel, and Jérôme Pacanowski (all from the Antigen Presentation by Dendritic Cell Team, Cochin Institute, Paris) and Martine Sinet (INSERM E0109, Le Kremlin-Bicêtre, France), as well as all members of the Dendritic Cells Workgroup from the Agence Nationale de la Recherche contre le SIDA et les hépatites virales (ANRS, Actions coordonnées 19 and 31), for stimulating discussions; and Marc Dalod (Centre d’Immunologie de Marseille, Luminy, Marseille, France), Rémi Cheynier and Stéphanie Beq (both from the Pasteur Institute, Paris) for greatly improving the manuscript. Work sponsored by the ANRS and Sidaction.

Received March 4, 2006; revised May 3, 2006; accepted July 5, 2006.


arrow
REFERENCES
 
    1
  1. Isaacs, A., Lindenmann, J. (1957) Virus interference. I. The interferon Proc. R. Soc. Lond. B. Biol. Sci. 147,258-267[Medline]
  2. 2
  3. Pestka, S., Krause, C. D., Sarkar, D., Walter, M. R., Shi, Y., Fisher, P. B. (2004) Interleukin-10 and related cytokines and receptors Annu. Rev. Immunol. 22,929-979[CrossRef][Medline]
  4. 3
  5. Tough, D. F. (2004) Type I interferon as a link between innate and adaptive immunity through dendritic cell stimulation Leuk. Lymphoma 45,257-264[CrossRef][Medline]
  6. 4
  7. Lebon, P. (1997) Interférons et maladies infectieuses Encyclopedie Medico-Chirurgicale Vol. 8-006-10,1-8 Elsevier Paris.
  8. 5
  9. Sheppard, P., Kindsvogel, W., Xu, W., Henderson, K., Schlutsmeyer, S., Whitmore, T. E., Kuestner, R., Garrigues, U., Birks, C., Roraback, J., et al (2003) IL-28, IL-29 and their class II cytokine receptor IL-28R Nat. Immunol. 4,63-68[CrossRef][Medline]
  10. 6
  11. Kotenko, S. V., Gallagher, G., Baurin, V. V., Lewis-Antes, A., Shen, M., Shah, N. K., Langer, J. A., Sheikh, F., Dickensheets, H., Donnelly, R. P. (2003) IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex Nat. Immunol. 4,69-77[CrossRef][Medline]
  12. 7
  13. Fauconnier, B. (1971) Effect of an anti-interferon serum on experimental viral pathogenicity in vivo Pathol. Biol. (Paris) 19,575-578[Medline]
  14. 8
  15. Gresser, I., Tovey, M. G., Bandu, M. E., Maury, C., Brouty-Boye, D. (1976) Role of interferon in the pathogenesis of virus diseases in mice as demonstrated by the use of anti-interferon serum. I. Rapid evolution of encephalomyocarditis virus infection J. Exp. Med. 144,1305-1315[Abstract/Free Full Text]
  16. 9
  17. Gresser, I., Tovey, M. G., Maury, C., Bandu, M. T. (1976) Role of interferon in the pathogenesis of virus diseases in mice as demonstrated by the use of anti-interferon serum. II. Studies with herpes simplex, Moloney sarcoma, vesicular stomatitis, Newcastle disease, and influenza viruses J. Exp. Med. 144,1316-1323[Abstract/Free Full Text]
  18. 10
  19. Muller, U., Steinhoff, U., Reis, L. F., Hemmi, S., Pavlovic, J., Zinkernagel, R. M., Aguet, M. (1994) Functional role of type I and type II interferons in antiviral defense Science 264,1918-1921[Abstract/Free Full Text]
  20. 11
  21. Pol, S., Vallet-Pichard, A., Fontaine, H. (2002) Hepatitis C and human immune deficiency coinfection at the era of highly active antiretroviral therapy J. Viral Hepat. 9,1-8[CrossRef][Medline]
  22. 12
  23. Khatissian, E., Tovey, M. C., Cumont, M. C., Manceaux, V., Lebon, P., Montagnier, L., Hurtrel, B., Chakrabarti, L. (1996) The relationship between the interferon alpha response and viral burden in primary SIV infection AIDS Res. Hum. Retroviruses 12,1273-1278[Medline]
  24. 13
  25. Abel, K., Compton, L., Rourke, T., Montefiori, D., Lu, D., Rothaeusler, K., Fritts, L., Bost, K., Miller, C. J. (2003) Simian-human immunodeficiency virus SHIV89.6-induced protection against intravaginal challenge with pathogenic SIVmac239 is independent of the route of immunization and is associated with a combination of cytotoxic T-lymphocyte and alpha interferon responses J. Virol. 77,3099-3118[Abstract/Free Full Text]
  26. 14
  27. Abel, K., Rocke, D. M., Chohan, B., Fritts, L., Miller, C. J. (2005) Temporal and anatomic relationship between virus replication and cytokine gene expression after vaginal simian immunodeficiency virus infection J. Virol. 79,12164-12172[Abstract/Free Full Text]
  28. 15
  29. Kamga, I., Develioglu, L., Lichtner, M., Kahi, S., Marañón, C., Deveau, C., Meyer, L., Goujard, C., Sinet, M., Lebon, P., et al (2005) Type I interferon production is profoundly impaired in primary HIV-1 infection J. Infect. Dis. 192,303-310[CrossRef][Medline]
  30. 16
  31. Lopez, C., Fitzgerald, P. A., Siegal, F. P. (1983) Severe acquired immune deficiency syndrome in male homosexuals: diminished capacity to make interferon-alpha in vitro associated with severe opportunistic infections J. Infect. Dis. 148,962-966[Medline]
  32. 17
  33. Siegal, F. P., Lopez, C., Fitzgerald, P. A., Shah, K., Baron, P., Leiderman, I. Z., Imperato, D., Landesman, S. (1986) Opportunistic infections in acquired immune deficiency syndrome result from synergistic defects of both the natural and adaptive components of cellular immunity J. Clin. Invest. 78,115-123[Medline]
  34. 18
  35. Howell, D. M., Feldman, S. B., Kloser, P., Fitzgerald-Bocarsly, P. (1994) Decreased frequency of functional natural interferon-producing cells in peripheral blood of patients with the acquired immune deficiency syndrome Clin. Immunol. Immunopathol. 71,223-230[CrossRef][Medline]
  36. 19
  37. Ferbas, J. J., Toso, J. F., Logar, A. J., Navratil, J. S., Rinaldo, C. R. (1994) CD4+ blood dendritic cells are potent producers of IFN-{alpha} in response to in vitro HIV infection J. Immunol. 152,4649-4662[Abstract]
  38. 20
  39. Ferbas, J., Navratil, J., Logar, A., Rinaldo, C. (1995) Selective decrease in human immunodeficiency virus type 1 (HIV-1)-induced alpha interferon production by peripheral blood mononuclear cells during HIV-1 infection Clin. Diagn. Lab. Immunol. 2,138-142[Medline]
  40. 21
  41. Feldman, S. B., Milone, M. C., Kloser, P., Fitzgerald-Bocarsly, P. (1995) Functional deficiencies in two distinct interferon alpha-producing cell populations in peripheral blood mononuclear cells from human immunodeficiency virus seropositive patients J. Leukoc. Biol. 57,214-220[Abstract]
  42. 22
  43. Chehimi, J., Campbell, D. E., Azzoni, L., Bacheller, D., Papasavvas, E., Jerandi, G., Mounzer, K., Kostman, J., Trinchieri, G., Montaner, L. J. (2002) Persistent decreases in blood plasmacytoid dendritic cell number and function despite effective highly active antiretroviral therapy and increased blood myeloid dendritic cells in HIV-infected individuals J. Immunol. 168,4796-4801[Abstract/Free Full Text]
  44. 23
  45. Anthony, D. D., Yonkers, N. L., Post, A. B., Asaad, R., Heinzel, F. P., Lederman, M. M., Lehmann, P. V., Valdez, H. (2004) Selective impairments in dendritic cell-associated function distinguish hepatitis C virus and HIV infection J. Immunol. 172,4907-4916[Abstract/Free Full Text]
  46. 24
  47. Soumelis, V., Scott, I., Gheyas, F., Bouhour, D., Cozon, G., Cotte, L., Huang, L., Levy, J. A., Liu, Y. J. (2001) Depletion of circulating natural type 1 interferon-producing cells in HIV-infected AIDS patients Blood 98,906-912[Abstract/Free Full Text]
  48. 25
  49. Vanhems, P., Voirin, N., Hirschel, B., Cooper, D. A., Vizzard, J., Carr, A., Perrin, L. (2003) Brief report: incubation and duration of specific symptoms at acute retroviral syndrome as independent predictors of progression to AIDS J. Acquir. Immune Defic. Syndr. 32,542-544[Medline]
  50. 26
  51. Perrin, L. (1999) Primary HIV infection Antivir. Ther. 4(Suppl 3),13-18[Medline]
  52. 27
  53. Finke, J. S., Shodell, M., Shah, K., Siegal, F. P., Steinman, R. M. (2004) Dendritic cell numbers in the blood of HIV-1 infected patients before and after changes in antiretroviral therapy J. Clin. Immunol. 24,647-652[CrossRef][Medline]
  54. 28
  55. Siegal, F. P., Fitzgerald-Bocarsly, P., Holland, B. K., Shodell, M. (2001) Interferon-alpha generation and immune reconstitution during antiretroviral therapy for human immunodeficiency virus infection AIDS 15,1603-1612[CrossRef][Medline]
  56. 29
  57. Feldman, S., Stein, D., Amrute, S., Denny, T., Garcia, Z., Kloser, P., Sun, Y., Megjugorac, N., Fitzgerald-Bocarsly, P. (2001) Decreased interferon-alpha production in HIV-infected patients correlates with numerical and functional deficiencies in circulating type 2 dendritic cell precursors Clin. Immunol. 101,201-210[CrossRef][Medline]
  58. 30
  59. Sanhadji, K., Leissner, P., Firouzi, R., Pelloquin, F., Kehrli, L., Marigliano, M., Calenda, V., Ottmann, M., Tardy, J. C., Mehtali, M., et al (1997) Experimental gene therapy: the transfer of Tat-inducible interferon genes protects human cells against HIV-1 challenge in vitro and in vivo in severe combined immunodeficient mice AIDS 11,977-986[CrossRef][Medline]
  60. 31
  61. Lapenta, C., Santini, S. M., Proietti, E., Rizza, P., Logozzi, M., Spada, M., Parlato, S., Fais, S., Pitha, P. M., Belardelli, F. (1999) Type I interferon is a powerful inhibitor of in vivo HIV-1 infection and preserves human CD4(+) T cells from virus-induced depletion in SCID mice transplanted with human cells Virology 263,78-88[CrossRef][Medline]
  62. 32
  63. Vieillard, V., Jouveshomme, S., Leflour, N., Jean-Pierre, E., Debre, P., De Maeyer, E., Autran, B. (1999) Transfer of human CD4(+) T lymphocytes producing beta interferon in Hu-PBL-SCID mice controls human immunodeficiency virus infection J. Virol. 73,10281-10288[Abstract/Free Full Text]
  64. 33
  65. Gurney, K. B., Colantonio, A. D., Blom, B., Spits, H., Uittenbogaart, C. H. (2004) Endogenous IFN-alpha production by plasmacytoid dendritic cells exerts an antiviral effect on thymic HIV-1 infection J. Immunol. 173,7269-7276[Abstract/Free Full Text]
  66. 34
  67. Beignon, A.S., McKenna, K., Skoberne, M., Manches, O., Dasilva, I., Kavanagh, D.G., Larsson, M., Gorelick, R.J., Lifson, J.D., Bhardwaj, N. (2005) Endocytosis of HIV-1 activates plasmacytoid dendritic cells via toll-like receptor-viral RNA interactions J. Clin. Invest. 115,3265-3275[CrossRef][Medline]
  68. 35
  69. Herbeuval, J. P., Hardy, A. W., Boasso, A., Anderson, S. A., Dolan, M. J., Dy, M., Shearer, G. M. (2005) Regulation of TNF-related apoptosis-inducing ligand on primary CD4+ T cells by HIV-1: role of type I IFN-producing plasmacytoid dendritic cells Proc. Natl. Acad. Sci. USA 102,13974-13979[Abstract/Free Full Text]
  70. 36
  71. Garcia-Sastre, A., Biron, C. A. (2006) Type 1 interferons and the virus-host relationship: a lesson in detente Science 312,879-882[Abstract/Free Full Text]
  72. 37
  73. Der, S. D., Zhou, A., Williams, B. R., Silverman, R. H. (1998) Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays Proc. Natl. Acad. Sci. USA 95,15623-15628[Abstract/Free Full Text]
  74. 38
  75. Haller, O., Kochs, G. (2002) Interferon-induced mx proteins: dynamin-like GTPases with antiviral activity Traffic 3,710-717[CrossRef][Medline]
  76. 39
  77. Marie, I., Durbin, J. E., Levy, D. E. (1998) Differential viral induction of distinct interferon-alpha genes by positive feedback through interferon regulatory factor-7 EMBO J. 17,6660-6669[CrossRef][Medline]
  78. 40
  79. Dalod, M., Hamilton, T., Salomon, R., Salazar-Mather, T. P., Henry, S. C., Hamilton, J. D., Biron, C. A. (2003) Dendritic cell responses to early murine cytomegalovirus infection: subset functional specialization and differential regulation by interferon alpha/beta J. Exp. Med. 197,885-898[Abstract/Free Full Text]
  80. 41
  81. Biron, C. A. (2001) Interferons alpha and beta as immune regulators–a new look Immunity 14,661-664[CrossRef][Medline]
  82. 42
  83. Le Bon, A., Durand, V., Kamphuis, E., Thompson, C., Bulfone-Paus, S., Rossmann, C., Kalinke, U., Tough, D. F. (2006) Direct stimulation of T cells by type I IFN enhances the CD8+ T cell response during cross-priming J. Immunol. 176,4682-4689[Abstract/Free Full Text]
  84. 43
  85. Aichele, P., Unsoeld, H., Koschella, M., Schweier, O., Kalinke, U., Vucikuja, S. (2006) CD8 T cells specific for lymphocytic choriomeningitis virus require type I IFN receptor for clonal expansion J. Immunol. 176,4525-4529[Abstract/Free Full Text]
  86. 44
  87. Thompson, L. J., Kolumam, G. A., Thomas, S., Murali-Krishna, K. (2006) Innate inflammatory signals induced by various pathogens differentially dictate the IFN-I dependence of CD8 T cells for clonal expansion and memory formation J. Immunol. 177,1746-1754[Abstract/Free Full Text]
  88. 45
  89. Marrack, P., Kappler, J., Mitchell, T. (1999) Type I interferons keep activated T cells alive J. Exp. Med. 189,521-530[Abstract/Free Full Text]
  90. 46
  91. Schwartz, O., Marechal, V., Le Gall, S., Lemonnier, F., Heard, J. M. (1996) Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 Nef protein Nat. Med. 2,338-342[CrossRef][Medline]
  92. 47
  93. Andrieu, M., Chassin, D., Desoutter, J. F., Bouchaert, I., Hanau, D., Guillet, J. G., Hosmalin, A. (2001) HIV-1 Nef protein induces a down-regulation of the dendritic cell surface expression of MHC class I and impairs antigen presentation to CTL AIDS Res. Hum. Retroviruses 17,1365-1370[CrossRef][Medline]
  94. 48
  95. Le Bon, A., Etchart, N., Rossmann, C., Ashton, M., Hou, S., Gewert, D., Borrow, P., Tough, D. F. (2003) Cross-priming of CD8+ T cells stimulated by virus-induced type I interferon Nat. Immunol. 4,1009-1015[CrossRef][Medline]
  96. 49
  97. Rock, K. L., Shen, L. (2005) Cross-presentation: underlying mechanisms and role in immune surveillance Immunol. Rev. 207,166-183[CrossRef][Medline]
  98. 50
  99. Chen, W., Masterman, K. A., Basta, S., Mansour Haeryfar, S. M., Dimopoulos, N., Knowles, B., Bennink, J. R., Yewdell, J. W. (2004) Cross-priming of CD8+ T cells by viral and tumor antigens is a robust phenomenon Eur. J. Immunol. 34,194-199[CrossRef][Medline]
  100. 51
  101. Ackerman, A. L., Cresswell, P. (2004) Cellular mechanisms governing cross-presentation of exogenous antigens Nat. Immunol. 5,678-684[CrossRef][Medline]
  102. 52
  103. Lizee, G., Basha, G., Tiong, J., Julien, J. P., Tian, M., Biron, K. E., Jefferies, W. A. (2003) Control of dendritic cell cross-presentation by the major histocompatibility complex class I cytoplasmic domain Nat. Immunol. 4,1065-1073[CrossRef][Medline]
  104. 53
  105. Marañón, C., Desoutter, J. F., Hoeffel, G., Cohen, W., Hanau, D., Hosmalin, A. (2004) Dendritic cells cross-present HIV antigens from live as well as apoptotic infected CD4+ T lymphocytes Proc. Natl. Acad. Sci. USA 101,6092-6097[Abstract/Free Full Text]
  106. 54
  107. Poli, G., Orenstein, J. M., Kinter, A., Folks, T. M., Fauci, A. S. (1989) Interferon-alpha but not AZT suppresses HIV expression in chronically infected cell lines Science 244,575-577[Abstract/Free Full Text]
  108. 55
  109. Bednarik, D. P., Mosca, J. D., Raj, N. B., Pitha, P. M. (1989) Inhibition of human immunodeficiency virus (HIV) replication by HIV-trans-activated alpha 2-interferon Proc. Natl. Acad. Sci. USA 86,4958-4962[Abstract/Free Full Text]
  110. 56
  111. Gendelman, H. E., Baca, L. M., Turpin, J., Kalter, D. C., Hansen, B., Orenstein, J. M., Dieffenbach, C. W., Friedman, R. M., Meltzer, M. S. (1990) Regulation of HIV replication in infected monocytes by IFN-alpha. Mechanisms for viral restriction J. Immunol. 145,2669-2676[Abstract]
  112. 57
  113. Meylan, P. R., Guatelli, J. C., Munis, J. R., Richman, D. D., Kornbluth, R. S. (1993) Mechanisms for the inhibition of HIV replication by interferons-alpha, -beta, and -gamma in primary human macrophages Virology 193,138-148[CrossRef][Medline]
  114. 58
  115. Shirazi, Y., Pitha, P. M. (1993) Interferon alpha-mediated inhibition of human immunodeficiency virus type 1 provirus synthesis in T-cells Virology 193,303-312[CrossRef][Medline]
  116. 59
  117. Agy, M. B., Acker, R. L., Sherbert, C. H., Katze, M. G. (1995) Interferon treatment inhibits virus replication in HIV-1- and SIV-infected CD4+ T-cell lines by distinct mechanisms: evidence for decreased stability and aberrant processing of HIV-1 proteins Virology 214,379-386[CrossRef][Medline]
  118. 60
  119. Vieillard, V., Lauret, E., Maguer, V., Jacomet, C., Rozenbaum, W., Gazzolo, L., De Maeyer, E. (1995) Autocrine interferon-beta synthesis for gene therapy of HIV infection: increased resistance to HIV-1 in lymphocytes from healthy and HIV-infected individuals AIDS 9,1221-1228[Medline]
  120. 61
  121. Baca, L. M., Genis, P., Kalvakolanu, D., Sen, G., Meltzer, M. S., Zhou, A., Silverman, R., Gendelman, H. E. (1994) Regulation of interferon-alpha-inducible cellular genes in human immunodeficiency virus-infected monocytes J. Leukoc. Biol. 55,299-309[Abstract]
  122. 62
  123. Schroder, H. C., Kelve, M., Muller, W. E. (1994) The 2-5A system and HIV infection Prog. Mol. Subcell. Biol. 14,176-197[Medline]
  124. 63
  125. Schroder, H. C., Suhadolnik, R. J., Pfleiderer, W., Charubala, R., Muller, W. E. (1992) (2'-5') Oligoadenylate and intracellular immunity against retrovirus infection Int. J. Biochem. 24,55-63[CrossRef][Medline]
  126. 64
  127. Hengel, H., Koszinowski, U.H., Conzelmann, K.K. (2005) Viruses know it all: new insights into IFN networks Trends Immunol. 26,396-401[CrossRef][Medline]
  128. 65
  129. Sgarbanti, M., Borsetti, A., Moscufo, N., Bellocchi, M. C., Ridolfi, B., Nappi, F., Marsili, G., Marziali, G., Coccia, E. M., Ensoli, B., et al (2002) Modulation of human immunodeficiency virus 1 replication by interferon regulatory factors J. Exp. Med. 195,1359-1370[Abstract/Free Full Text]
  130. 66
  131. Maitra, R. K., McMillan, N. A., Desai, S., McSwiggen, J., Hovanessian, A. G., Sen, G., Williams, B. R., Silverman, R. H. (1994) HIV-1 TAR RNA has an intrinsic ability to activate interferon-inducible enzymes Virology 204,823-827[CrossRef][Medline]
  132. 67
  133. Martinand, C., Montavon, C., Salehzada, T., Silhol, M., Lebleu, B., Bisbal, C. (1999) RNase L inhibitor is induced during human immunodeficiency virus type 1 infection and down regulates the 2-5A/RNase L pathway in human T cells J. Virol. 73,290-296[Abstract/Free Full Text]
  134. 68
  135. McMillan, N. A., Chun, R. F., Siderovski, D. P., Galabru, J., Toone, W. M., Samuel, C. E., Mak, T. W., Hovanessian, A. G., Jeang, K. T., Williams, B. R. (1995) HIV-1 Tat directly interacts with the interferon-induced, double-stranded RNA-dependent kinase, PKR Virology 213,413-424[CrossRef][Medline]
  136. 69
  137. Chendrimada, T. P., Gregory, R. I., Kumaraswamy, E., Norman, J., Cooch, N., Nishikura, K., Shiekhattar, R. (2005) TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing Nature 436,740-744[CrossRef][Medline]
  138. 70
  139. Haase, A. D., Jaskiewicz, L., Zhang, H., Laine, S., Sack, R., Gatignol, A., Filipowicz, W. (2005) TRBP, a regulator of cellular PKR and HIV-1 virus expression, interacts with Dicer and functions in RNA silencing EMBO Rep. 6,961-967[Medline]
  140. 71
  141. Gatignol, A., Laine, S., Clerzius, G. (2005) Dual role of TRBP in HIV replication and RNA interference: viral diversion of a cellular pathway or evasion from antiviral immunity? Retrovirology 2,65[CrossRef][Medline]
  142. 72
  143. Endo-Munoz, L., Warby, T., Harrich, D., McMillan, N. A. (2005) Phosphorylation of HIV Tat by PKR increases interaction with TAR RNA and enhances transcription Virol. J. 2,17-30[CrossRef][Medline]
  144. 73
  145. Lum, J. J., Pilon, A. A., Sanchez-Dardon, J., Phenix, B. N., Kim, J. E., Mihowich, J., Jamison, K., Hawley-Foss, N., Lynch, D. H., Badley, A. D. (2001) Induction of cell death in HIV-infected macrophages and resting memory CD4 T cells by TRAIL-Apo2L J. Virol. 75,11128-11136[Abstract/Free Full Text]
  146. 74
  147. Lichtner, M., Marañón, C., Vidalain, P. O., Hanau, D., Lebon, P., Burgart, M., Rouzioux, C., Vullo, V., Yagita, H., Rabourdin-Combe, C., et al (2004) HIV-1 infected dendritic cells induce apoptotic death in infected and uninfected primary CD4+ T lymphocytes AIDS Res. Hum. Retroviruses 20,175-182[CrossRef][Medline]
  148. 75
  149. Herbeuval, J. P., Boasso, A., Grivel, J. C., Hardy, A. W., Anderson, S. A., Dolan, M. J., Chougnet, C., Lifson, J. D., Shearer, G. M. (2005) TNF-related apoptosis-inducing ligand (TRAIL) in HIV-1-infected patients and its in vitro production by antigen-presenting cells Blood 105,2458-2464
  150. 76
  151. Vieillard, V., Strominger, J. L., Debre, P. (2005) NK cytotoxicity against CD4+ T cells during HIV-1 infection: a gp41 peptide induces the expression of an NKp44 ligand Proc. Natl. Acad. Sci. USA 102,10981-10986[Abstract/Free Full Text]
  152. 77
  153. Estaquier, J., Idziorek, T., de Bels, F., Barre-Sinoussi, F., Hurtrel, B., Aubertin, A. M., Venet, A., Mehtali, M., Muchmore, E., Michel, P., et al (1994) Programmed cell death and AIDS: significance of T-cell apoptosis in pathogenic and nonpathogenic primate lentiviral infections Proc. Natl. Acad. Sci. USA 91,9431-9435[Abstract/Free Full Text]
  154. 78
  155. Miura, Y., Misawa, N., Maeda, N., Inagaki, Y., Tanaka, Y., Ito, M., Kayagaki, N., Yamamoto, N., Yagita, H., Mizusawa, H., et al (2001) Critical contribution of TNF-related apoptosis-inducing ligand (TRAIL) to apoptosis of human CD4+ T cells in HIV-1 infected hu-PBL-NOD-SCID mice J. Exp. Med. 193,651-659[Abstract/Free Full Text]
  156. 79
  157. Keir, M. E., Stoddart, C. A., Linquist-Stepps, V., Moreno, M. E., McCune, J. M. (2002) IFN-alpha secretion by type 2 predendritic cells up-regulates MHC class I in the HIV-1-infected thymus J. Immunol. 168,325-331[Abstract/Free Full Text]
  158. 80
  159. Keir, M. E., Rosenberg, M. G., Sandberg, J. K., Jordan, K. A., Wiznia, A., Nixon, D. F., Stoddart, C. A., McCune, J. M. (2002) Generation of CD3+CD8 low thymocytes in the HIV type 1-infected thymus J. Immunol. 169,2788-2796[Abstract/Free Full Text]
  160. 81
  161. Zagury, D., Lachgar, A., Chams, V., Fall, L. S., Bernard, J., Zagury, J. F., Bizzini, B., Gringeri, A., Santagostino, E., Rappaport, J., et al (1998) Interferon alpha and Tat involvement in the immunosuppression of uninfected T cells and C-C chemokine decline in AIDS Proc. Natl. Acad. Sci. USA 95,3851-3856[Abstract/Free Full Text]
  162. 82
  163. Coulaud, I. P., Gougeon, M. L., Gomard, E., Descamps, D., Lebon, P., Aboulker, J. P., Bizzini, B., Zagury, D. (1997) A placebo-controlled clinical phase I trial with combined anti-HIV-1 and anti-interferon-alpha immunization AIDS 11,937-938[Medline]
  164. 83
  165. Lane, H. C., Davey, V., Kovacs, J. A., Feinberg, J., Metcalf, J. A., Herpin, B., Walker, R., Deyton, L., Davey, R. T., Jr, Falloon, J., et al (1990) Interferon-alpha in patients with asymptomatic human immunodeficiency virus (HIV) infection. A randomized, placebo-controlled trial Ann. Intern. Med. 112,805-811[Abstract/Free Full Text]
  166. 84
  167. Riviere, Y., Gresser, I., Guillon, J. C., Tovey, M. G. (1977) Inhibition by anti-interferon serum of lymphocytic choriomeningitis virus disease in suckling mice Proc. Natl. Acad. Sci. USA 74,2135-2139[Abstract/Free Full Text]
  168. 85
  169. Hahm, B., Trifilo, M.J., Zuniga, E.I., Oldstone, M.B. (2005) Viruses evade the immune system through type I interferon-mediated STAT2-dependent, but STAT1-independent, signaling Immunity 22,247-57[CrossRef][Medline]
  170. 86
  171. McNally, J.M., Zarozinski, C.C., Lin, M.Y., Brehm, M.A., Chen, H.D., Welsh, R.M. (2001) Attrition of bystander CD8 T cells during virus-induced T-cell and interferon responses J Virol 75,5965-76[Abstract/Free Full Text]
  172. 87
  173. Bahl, K., Kim, S.K., Calcagno, C., Ghersi, D., Puzone, R., Celada, F., Selin, L.K., Welsh, R.M. (2006) IFN-induced attrition of CD8 T cells in the presence or absence of cognate antigen during the early stages of viral infections J Immunol 176,4284-95[Abstract/Free Full Text]
  174. 88
  175. Blanco, P., Palucka, A. K., Gill, M., Pascual, V., Banchereau, J. (2001) Induction of dendritic cell differentiation by IFN-alpha in systemic lupus erythematosus Science 294,1540-1543[Abstract/Free Full Text]
  176. 89
  177. Banchereau, J., Paczesny, S., Blanco, P., Bennett, L., Pascual, V., Fay, J., Palucka, A. K. (2003) Dendritic cells: controllers of the immune system and a new promise for immunotherapy Ann. N. Y. Acad. Sci. 987,180-187[Medline]
  178. 90
  179. Perussia, B., Fanning, V., Trinchieri, G. (1985) A leukocyte subset bearing HLA-DR antigens is responsible for in vitro alpha interferon production in response to viruses Nat. Immun. Cell Growth Regul. 4,120-137[Medline]
  180. 91
  181. Fitzgerald-Bocarsly, P., Feldman, M., Mendelsohn, M., Curl, S., Lopez, C. (1988) Human mononuclear cells which produce interferon-alpha during NK(HSV-FS) assays are HLA-DR positive cells distinct from cytolytic natural killer effectors J. Leukoc. Biol. 43,323-334[Abstract]
  182. 92
  183. Chehimi, J., Starr, S. E., Kawashima, H., Miller, D. S., Trinchieri, G., Perussia, B., Bandyopadhyay, S. (1989) Dendritic cells and IFN-alpha-producing cells are two functionally distinct non-B, non-monocytic HLA-DR+ cell subsets in human peripheral blood Immunology 68,486-490[Medline]
  184. 93
  185. Siegal, F., Kadowaki, N., Shodell, M., Fitzgerald-Bocarsly, P., Shah, K., Ho, S., Antonenko, S., Liu, Y. (1999) The nature of the principal type 1 interferon-producing cells in human blood Science 284,1835-1837[Abstract/Free Full Text]
  186. 94
  187. Grouard, G., Rissoan, M.-C., Filgueira, L., Durand, I., Banchereau, J., Liu, Y.-J. (1997) The enigmatic plasmacytoid T cells develop into dendritic cells with Interleukin 3 and CD40-ligand J. Exp. Med. 185,1101-1111[Abstract/Free Full Text]
  188. 95
  189. Rissoan, M. C., Soumelis, V., Kadowaki, N., Grouard, G., Briere, F., de Waal Malefyt, R., Liu, Y. J. (1999) Reciprocal control of T helper cell and dendritic cell differentiation Science 283,1183-1186[Abstract/Free Full Text]
  190. 96
  191. Cella, M., Jarrossay, D., Facchetti, F., Alebardi, O., Nakajima, H., Lanzavecchia, A., Colonna, M. (1999) Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon Nat. Med. 5,919-923[CrossRef][Medline]
  192. 97
  193. Dzionek, A., Sohma, Y., Nagafune, J., Cella, M., Colonna, M., Facchetti, F., Gunther, G., Johnston, I., Lanzavecchia, A., Nagasaka, T., et al (2001) BDCA-2, a novel plasmacytoid dendritic cell-specific type II C-type lectin, mediates antigen capture and is a potent inhibitor of interferon alpha/beta induction J. Exp. Med. 194,1823-1834[Abstract/Free Full Text]
  194. 98
  195. Asselin-Paturel, C., Boonstra, A., Dalod, M., Durand, I., Yessaad, N., Dezutter-Dambuyant, C., Vicari, A., O'Garra, A., Biron, C., Briere, F., et al (2001) Mouse type I IFN-producing cells are immature APCs with plasmacytoid morphology Nat. Immunol. 2,1144-1150[CrossRef][Medline]
  196. 99
  197. Bjorck, P. (2001) Isolation and characterization of plasmacytoid dendritic cells from Flt3 ligand and granulocyte-macrophage colony-stimulating factor-treated mice Blood 98,3520-3526[Abstract/Free Full Text]
  198. 100
  199. Nakano, H., Yanagita, M., Gunn, M.D. (2001) CD11c(+)B220(+)Gr-1(+) cells in mouse lymph nodes and spleen display characteristics of plasmacytoid dendritic cells J Exp Med 194,1171-8[Abstract/Free Full Text]
  200. 101
  201. Shortman, K., Heath, W. R. (2001) Immunity or tolerance? That is the question for dendritic cells Nat. Immunol. 2,988-989[CrossRef][Medline]
  202. 102
  203. Colonna, M., Trinchieri, G., Liu, Y. J. (2004) Plasmacytoid dendritic cells in immunity Nat. Immunol. 5,1219-1226[CrossRef][Medline]
  204. 103
  205. Asselin-Paturel, C., Brizard, G., Pin, J. J., Briere, F., Trinchieri, G. (2003) Mouse strain differences in plasmacytoid dendritic cell frequency and function revealed by a novel monoclonal antibody J. Immunol. 171,6466-6477[Abstract/Free Full Text]
  206. 104
  207. Dalod, M., Salazar-Mather, T. P., Malmgaard, L., Lewis, C., Asselin-Paturel, C., Briere, F., Trinchieri, G., Biron, C. A. (2002) Interferon alpha/beta and interleukin 12 responses to viral infections: pathways regulating dendritic cell cytokine expression in vivo J. Exp. Med. 195,517-528[Abstract/Free Full Text]
  208. 105
  209. Krug, A., French, A. R., Barchet, W., Fischer, J. A., Dzionek, A., Pingel, J. T., Orihuela, M. M., Akira, S., Yokoyama, W. M., Colonna, M. (2004) TLR9-dependent recognition of MCMV by IPC and DC generates coordinated cytokine responses that activate antiviral NK cell function Immunity 21,107-119[CrossRef][Medline]
  210. 106
  211. Barchet, W., Krug, A., Cella, M., Newby, C., Fischer, J. A., Dzionek, A., Pekosz, A., Colonna, M. (2005) Dendritic cells respond to influenza virus through TLR7- and PKR-independent pathways Eur. J. Immunol. 35,236-242[CrossRef][Medline]
  212. 107
  213. Ito, T., Kanzler, H., Duramad, O., Cao, W., Liu, Y. J. (2006) Specialization, kinetics, and repertoire of type 1 interferon responses by human plasmacytoid predendritic cells Blood 107,2423-2431[Abstract/Free Full Text]
  214. 108
  215. Yonezawa, A., Morita, R., Takaori-Kondo, A., Kadowaki, N., Kitawaki, T., Hori, T., Uchiyama, T. (2003) Natural alpha interferon-producing cells respond to human immunodeficiency virus type 1 with alpha interferon production and maturation into dendritic cells J. Virol. 77,3777-3784[Abstract/Free Full Text]
  216. 109
  217. Del Corno, M., Gauzzi, M. C., Penna, G., Belardelli, F., Adorini, L., Gessani, S. (2005) Human immunodeficiency virus type 1 gp120 and other activation stimuli are highly effective in triggering alpha interferon and CC chemokine production in circulating plasmacytoid but not myeloid dendritic cells J. Virol. 79,12597-12601[Abstract/Free Full Text]
  218. 110
  219. Cella, M., Facchetti, F., Lanzavecchia, A., Colonna, M. (2000) Plasmacytoid dendritic cells activated by influenza virus and CD40L drive a potent TH1 polarization Nat. Immunol. 1,305-310[CrossRef][Medline]
  220. 111
  221. Kadowaki, N., Antonenko, S., Lau, J., Liu, Y. (2000) Natural interferon {alpha}/ß-producing cells link innate and adaptive immunity J. Exp. Med. 192,219-225[Abstract/Free Full Text]
  222. 112
  223. Donaghy, H., Pozniak, A., Gazzard, B., Qazi, N., Gilmour, J., Gotch, F., Patterson, S. (2001) Loss of blood CD11c(+) myeloid and CD11c(–) plasmacytoid dendritic cells in patients with HIV-1 infection correlates with HIV-1 RNA virus load Blood 98,2574-2576[Abstract/Free Full Text]
  224. 113
  225. Pacanowski, J., Kahi, S., Baillet, M., Lebon, P., Deveau, C., Goujard, C., Meyer, L., Oksenhendler, E., Sinet, M., Hosmalin, A. (2001) Reduced blood CD123+ and CD11c+ dendritic cell numbers in primary HIV-1 infection Blood 98,3016-3021[Abstract/Free Full Text]
  226. 114
  227. Barron, M.A., Blyveis, N., Palmer, B.E., MaWhinney, S., Wilson, C.C. (2003) Influence of plasma viremia on defects in number and immunophenotype of blood dendritic cell subsets in human immunodeficiency virus 1-infected individuals J. Infect. Dis. 187,26-37[CrossRef][Medline]
  228. 115
  229. Azzoni, L., Rutstein, R. M., Chehimi, J., Farabaugh, M. A., Nowmos, A., Montaner, L. J. (2005) Dendritic and natural killer cell subsets associated with stable or declining CD4+ cell counts in treated HIV-1-infected children J. Infect. Dis. 191,1451-1459[CrossRef][Medline]
  230. 116
  231. Servet, C., Zitvogel, L., Hosmalin, A. (2002) Dendritic cells in innate immune responses against HIV Curr. Mol. Med. 2,739-756[CrossRef][Medline]
  232. 117
  233. Schmidt, B., Fujimura, S. H., Martin, J. N., Levy, J. A. (2006) Variations in plasmacytoid dendritic cell (PDC) and myeloid dendritic cell (MDC) levels in HIV-infected subjects on and off antiretroviral therapy J. Clin. Immunol. 26,55-64[CrossRef][Medline]
  234. 118
  235. Longman, R. S., Talal, A. H., Jacobson, I. M., Rice, C. M., Albert, M. L. (2005) Normal functional capacity in circulating myeloid and plasmacytoid dendritic cells in patients with chronic hepatitis C J. Infect. Dis. 192,497-503[CrossRef][Medline]
  236. 119
  237. Thiebot, H., Louache, F., Vaslin, B., de Revel, T., Neildez, O., Larghero, J., Vainchenker, W., Dormont, D., Le Grand, R. (2001) Early and persistent bone marrow hematopoiesis defect in simian/human immunodeficiency virus-infected macaques despite efficient reduction of viremia by highly active antiretroviral therapy during primary infection J. Virol. 75,11594-602[Abstract/Free Full Text]
  238. 120
  239. Thiebot, H., Vaslin, B., Derdouch, S., Bertho, J.M., Mouthon, F., Prost, S., Gras, G., Ducouret, P., Dormont, D., Le Grand, R. (2005) Impact of bone marrow hematopoiesis failure on T-cell generation during pathogenic simian immunodeficiency virus infection in macaques Blood 105,2403-2409
  240. 121
  241. Patterson, S., Rae, A., Hockey, N., Gilmour, J., Gotch, F. (2001) Plasmacytoid dendritic cells are highly susceptible to human immunodeficiency virus type 1 infection and release infectious virus J. Virol. 75,6710-6713[Abstract/Free Full Text]
  242. 122
  243. Schmidt, B., Scott, I., Whitmore, R. G., Foster, H., Fujimura, S., Schmitz, J., Levy, J. A. (2004) Low-level HIV infection of plasmacytoid dendritic cells: onset of cytopathic effects and cell death after PDC maturation Virology 329,280-288[Medline]
  244. 123
  245. Fong, L., Mengozzi, M., Abbey, N. W., Herndier, B. G., Engleman, E. G. (2002) Productive infection of plasmacytoid dendritic cells with human immunodeficiency virus type 1 is triggered by CD40 ligation J. Virol. 76,11033-11041[Abstract/Free Full Text]
  246. 124
  247. Donaghy, H., Gazzard, B., Gotch, F., Patterson, S. (2003) Dysfunction and infection of freshly isolated blood myeloid and plasmacytoid dendritic cells in patients infected with HIV-1 Blood 101,4505-4511[Abstract/Free Full Text]
  248. 125
  249. Foussat, A., Bouchet-Delbos, L., Berrebi, D., Durand-Gasselin, I., Coulomb-L'Hermine, A., Krzysiek, R., Galanaud, P., Levy, Y., Emilie, D. (2001) Deregulation of the expression of the fractalkine/fractalkine receptor complex in HIV-1-infected patients Blood 98,1678-1686[Abstract/Free Full Text]
  250. 126
  251. Lore, K., Sonnerborg, A., Brostrom, C., Goh, L. E., Perrin, L., McDade, H., Stellbrink, H. J., Gazzard, B., Weber, R., Napolitano, L. A., et al (2002) Accumulation of DC-SIGN+CD40+ dendritic cells with reduced CD80 and CD86 expression in lymphoid tissue during acute HIV-1 infection AIDS 16,683-692[CrossRef][Medline]
  252. 127
  253. Zimmer, M. I., Larregina, A. T., Castillo, C. M., Capuano, S., III, Falo, L. D., Jr, Murphey-Corb, M., Reinhart, T. A., Barratt-Boyes, S. M. (2002) Disrupted homeostasis of Langerhans cells and interdigitating dendritic cells in monkeys with AIDS Blood 99,2859-2868[Abstract/Free Full Text]
  254. 128
  255. McIlroy, D., Autran, B., Clauvel, J. -P., Oksenhendler, E., Debré, P., Hosmalin, A. (1998) Low CD83, but normal MHC class II and costimulatory molecule expression, on spleen dendritic cells from HIV+ patients AIDS Res. Hum. Retroviruses 14,505-513[Medline]
  256. 129
  257. McIlroy, D., Autran, B., Cheynier, R., Wain-Hobson, S., Clauvel, J.-P., Oksenhendler, E., Debre, P., Hosmalin, A. (1995) Dendritic cell and CD4+ T lymphocyte infection frequency in spleens of HIV-positive patients J. Virol. 69,4737-4745[Abstract]
  258. 130
  259. Steinman, R. M., Pack, M., Inaba, K. (1997) Dendritic cells in the T-cell areas of lymphoid organs Immunol. Rev. 156,25-37[CrossRef][Medline]
  260. 131
  261. Cox, K., North, M., Burke, M., Singhal, H., Renton, S., Aqel, N., Islam, S., Knight, S. C. (2005) Plasmacytoid dendritic cells (PDC) are the major DC subset innately producing cytokines in human lymph nodes J. Leukoc. Biol. 78,1142-1152[Abstract/Free Full Text]
  262. 132
  263. Penna, G., Sozzani, S., Adorini, L. (2001) Cutting edge: selective usage of chemokine receptors by plasmacytoid dendritic cells J. Immunol. 167,1862-1866[Abstract/Free Full Text]
  264. 133
  265. Facchetti, F., Vermi, W., Mason, D., Colonna, M. (2003) The plasmacytoid monocyte/interferon producing cells Virchows Arch. 443,703-717[CrossRef][Medline]
  266. 134
  267. Diacovo, T.G., Blasius, A.L., Mak, T.W., Cella, M., Colonna, M. (2005) Adhesive mechanisms governing interferon-producing cell recruitment into lymph nodes J Exp Med 202,687-696[Abstract/Free Full Text]
  268. 135
  269. Yoneyama, H., Matsuno, K., Zhang, Y., Nishiwaki, T., Kitabatake, M., Ueha, S., Narumi, S., Morikawa, S., Ezaki, T., Lu, B., et al (2004) Evidence for recruitment of plasmacytoid dendritic cell precursors to inflamed lymph nodes through high endothelial venules Int. Immunol. 16,915-928[Abstract/Free Full Text]
  270. 136
  271. Zou, W., Machelon, V., Coulomb-L'Hermin, A., Borvak, J., Nome, F., Isaeva, T., Wei, S., Krzysiek, R., Durand-Gasselin, I., Gordon, A., et al (2001) Stromal-derived factor-1 in human tumors recruits and alters the function of plasmacytoid precursor dendritic cells Nat. Med. 7,1339-1346[CrossRef][Medline]
  272. 137
  273. Vermi, W., Riboldi, E., Wittamer, V., Gentili, F., Luini, W., Marrelli, S., Vecchi, A., Franssen, J. D., Communi, D., Massardi, L., et al (2005) Role of ChemR23 in directing the migration of myeloid and plasmacytoid dendritic cells to lymphoid organs and inflamed skin J. Exp. Med. 201,509-515[Abstract/Free Full Text]
  274. 138
  275. Banchereau, J., Briere, F., Caux, C., Davoust, J., Lebecque, S., Liu, Y. J., Pulendran, B., Palucka, K. (2000) Immunobiology of dendritic cells Annu. Rev. Immunol. 18,767-811[CrossRef][Medline]
  276. 139
  277. Fonteneau, J. F., Larsson, M., Beignon, A. S., McKenna, K., Dasilva, I., Amara, A., Liu, Y. J., Lifson, J. D., Littman, D. R., Bhardwaj, N. (2004) Human immunodeficiency virus type 1 activates plasmacytoid dendritic cells and concomitantly induces the bystander maturation of myeloid dendritic cells J. Virol. 78,5223-5232[Abstract/Free Full Text]
  278. 140
  279. Asselin-Paturel, C., Brizard, G., Chemin, K., Boonstra, A., O'Garra, A., Vicari, A., Trinchieri, G. (2005) Type I interferon dependence of plasmacytoid dendritic cell activation and migration J. Exp. Med. 201,1157-1167[Abstract/Free Full Text]
  280. 141
  281. Penna, G., Vulcano, M., Roncari, A., Facchetti, F., Sozzani, S., Adorini, L. (2002) Cutting edge: differential chemokine production by myeloid and plasmacytoid dendritic cells J. Immunol. 169,6673-6676[Abstract/Free Full Text]
  282. 142
  283. Langenkamp, A., Nagata, K., Murphy, K., Wu, L., Lanzavecchia, A., Sallusto, F. (2003) Kinetics and expression patterns of chemokine receptors in human CD4+ T lymphocytes primed by myeloid or plasmacytoid dendritic cells Eur. J. Immunol. 33,474-482[CrossRef][Medline]
  284. 143
  285. Megjugorac, N. J., Young, H. A., Amrute, S. B., Olshalsky, S. L., Fitzgerald-Bocarsly, P. (2004) Virally stimulated plasmacytoid dendritic cells produce chemokines and induce migration of T and NK cells J. Leukoc. Biol. 75,504-514[Abstract/Free Full Text]
  286. 144
  287. Piqueras, B., Connolly, J., Freitas, H., Palucka, A. K., Banchereau, J. (2005) Upon viral exposure myeloid and plasmacytoid dendritic cells produce three waves of distinct chemokines to recruit immune effectors Blood. 107,2613-2618[Medline]
  288. 145
  289. Zou, W., Borvak, J., Wei, S., Isaeva, T., Curiel, D. T., Curiel, T. J. (2001) Reciprocal regulation of plasmacytoid dendritic cells and monocytes during viral infection Eur. J. Immunol. 31,3833-3839[CrossRef][Medline]
  290. 146
  291. Tasca, S., Tambussi, G., Nozza, S., Capiluppi, B., Zocchi, M. R., Soldini, L., Veglia, F., Poli, G., Lazzarin, A., Fortis, C. (2003) Escape of monocyte-derived dendritic cells of HIV-1 infected individuals from natural killer cell-mediated lysis AIDS 17,2291-2298[CrossRef][Medline]
  292. 147
  293. Gerosa, F., Gobbi, A., Zorzi, P., Burg, S., Briere, F., Carra, G., Trinchieri, G. (2005) The reciprocal interaction of NK cells with plasmacytoid or myeloid dendritic cells profoundly affects innate resistance functions J. Immunol. 174,727-734[Abstract/Free Full Text]
  294. 148
  295. Weiss, L., Donkova-Petrini, V., Caccavelli, L., Balbo, M., Carbonneil, C., Levy, Y. (2004) Human immunodeficiency virus-driven expansion of CD4+CD25+ Regulatory T cells Which Suppress HIV-specific CD4 T-cell Responses in HIV-infected Patients Blood 104,3249-3256[Abstract/Free Full Text]
  296. 149
  297. Aandahl, E. M., Michaelsson, J., Moretto, W. J., Hecht, F. M., Nixon, D. F. (2004) Human CD4+ CD25+ regulatory T cells control T-cell responses to human immunodeficiency virus and cytomegalovirus antigens J. Virol. 78,2454-2459[CrossRef][Medline]
  298. 150
  299. Kinter, A. L., Hennessey, M., Bell, A., Kern, S., Lin, Y., Daucher, M., Planta, M., McGlaughlin, M., Jackson, R., Ziegler, S. F., et al (2004) CD25(+)CD4(+) regulatory T cells from the peripheral blood of asymptomatic HIV-infected individuals regulate CD4(+) and CD8(+) HIV-specific T cell immune responses in vitro and are associated with favorable clinical markers of disease status J. Exp. Med. 200,331-343[Abstract/Free Full Text]
  300. 151
  301. Kornfeld, C., Ploquin, M. J., Pandrea, I., Faye, A., Onanga, R., Apetrei, C., Poaty-Mavoungou, V., Rouquet, P., Estaquier, J., Mortara, L., Desoutter, J.F., Butor, C., Le Grand, R., Roques, P., Simon, F., Barre-Sinoussi, F., Diop, O. M., Muller-Trutwin, M. C. (2005) Antiinflammatory profiles during primary SIV infection in African green monkeys are associated with protection against AIDS J. Clin. Invest. 115,1082-91[CrossRef][Medline]
  302. 152
  303. Andersson, J., Boasso, A., Nilsson, J., Zhang, R., Shire, N. J., Lindback, S., Shearer, G. M., Chougnet, C. A. (2005) The prevalence of regulatory T cells in lymphoid tissue is correlated with viral load in HIV-infected patients J. Immunol. 174,3143-3147[Abstract/Free Full Text]
  304. 153
  305. Estes, J. D., Li, Q., Reynolds, M. R., Wietgrefe, S., Duan, L., Schacker, T., Picker, L. J., Watkins, D. I., Lifson, J. D., Reilly, C., et al (2006) Premature induction of an immunosuppressive regulatory T cell response during acute simian immunodeficiency virus infection J. Infect. Dis. 193,703-712[CrossRef][Medline]
  306. 154
  307. Eggena, M. P., Barugahare, B., Jones, N., Okello, M., Mutalya, S., Kityo, C., Mugyenyi, P., Cao, H. (2005) Depletion of regulatory T cells in HIV infection is associated with immune activation J. Immunol. 174,4407-4414[Abstract/Free Full Text]
  308. 155
  309. Moseman, E. A., Liang, X., Dawson, A. J., Panoskaltsis-Mortari, A., Krieg, A. M., Liu, Y. J., Blazar, B. R., Chen, W. (2004) Human plasmacytoid dendritic cells activated by CpG oligodeoxynucleotides induce the generation of CD4+CD25+ regulatory T cells J. Immunol. 173,4433-4442[Abstract/Free Full Text]
  310. 156
  311. Gilliet, M., Liu, Y. J. (2002) Generation of human CD8 T regulatory cells by CD40 ligand-activated plasmacytoid dendritic cells J. Exp. Med. 195,695-704[Abstract/Free Full Text]
  312. 157
  313. Kawamura, K., Kadowaki, N., Kitawaki, T., Uchiyama, T. (2006) Virus-stimulated plasmacytoid dendritic cells induce CD4+ cytotoxic regulatory T cells Blood 107,1031-1038[Abstract/Free Full Text]
  314. 158
  315. Krathwohl, M. D., Schacker, T. W., Anderson, J. L. (2006) Abnormal presence of semimature dendritic cells that induce regulatory T cells in HIV-infected subjects J. Infect. Dis. 193,494-504[CrossRef][Medline]
  316. 159
  317. Smed-Sorensen, A., Lore, K., Vasudevan, J., Louder, M. K., Andersson, J., Mascola, J. R., Spetz, A. L., Koup, R. A. (2005) Differential susceptibility to human immunodeficiency virus type 1 infection of myeloid and plasmacytoid dendritic cells J. Virol. 79,8861-8869[Abstract/Free Full Text]
  318. 160
  319. Smed-Sorensen, A., Lore, K., Walther-Jallow, L., Andersson, J., Spetz, A. L. (2004) HIV-1-infected dendritic cells up-regulate cell surface markers but fail to produce IL-12 p70 in response to CD40 ligand stimulation Blood 104,2810-2817[Abstract/Free Full Text]
  320. 161
  321. Lore, K., Smed-Sorensen, A., Vasudevan, J., Mascola, J. R., Koup, R. A. (2005) Myeloid and plasmacytoid dendritic cells transfer HIV-1 preferentially to antigen-specific CD4+ T cells J. Exp. Med. 201,2023-2033[Abstract/Free Full Text]
  322. 162
  323. Pichyangkul, S., Endy, T. P., Kalayanarooj, S., Nisalak, A., Yongvanitchit, K., Green, S., Rothman, A. L., Ennis, F. A., Libraty, D. H. (2003) A blunted blood plasmacytoid dendritic cell response to an acute systemic viral infection is associated with increased disease severity J. Immunol. 171,5571-5578[Abstract/Free Full Text]
  324. 163
  325. Lichtner, M., Rossi, R., Mengoni, F., Vignoli, S., Colacchia, B., Massetti, A. P., Kamga, I., Hosmalin, A., Vullo, V., Mastroianni, C. M. (2006) Circulating dendritic cells and interferon-alpha production in patients with tuberculosis: correlation with clinical outcome and treatment response Clin. Exp. Immunol. 143,329-337[CrossRef][Medline]
  326. 164
  327. Tebas, P., Henry, K., Mondy, K., Deeks, S., Valdez, H., Cohen, C., Powderly, W. G. (2002) Effect of prolonged discontinuation of successful antiretroviral therapy on CD4+ T cell decline in human immunodeficiency virus-infected patients: implications for intermittent therapeutic strategies J. Infect. Dis. 186,851-854[CrossRef][Medline]
  328. 165
  329. Lafeuillade, A., Poggi, C., Hittinger, G., Counillon, E., Emilie, D. (2003) Predictors of plasma human immunodeficiency virus type 1 RNA control after discontinuation of highly active antiretroviral therapy initiated at acute infection combined with structured treatment interruptions and immune-based therapies J. Infect. Dis. 188,1426-1432[CrossRef][Medline]
  330. 166
  331. Maggiolo, F., Ripamonti, D., Gregis, G., Quinzan, G., Callegaro, A., Suter, F. (2004) Effect of prolonged discontinuation of successful antiretroviral therapy on CD4 T cells: a controlled, prospective trial AIDS 18,439-446[CrossRef][Medline]
  332. 167
  333. Thiebaut, R., Pellegrin, I., Chene, G., Viallard, J. F., Fleury, H., Moreau, J. F., Pellegrin, J. L., Blanco, P. (2005) Immunological markers after long-term treatment interruption in chronically HIV-1 infected patients with CD4 cell count above 400 x 10(6) cells/l AIDS 19,53-61[Medline]
  334. 168
  335. Deeks, S. G., Kitchen, C. M., Liu, L., Guo, H., Gascon, R., Narvaez, A. B., Hunt, P., Martin, J. N., Kahn, J. O., Levy, J., et al (2004) Immune activation set point during early HIV infection predicts subsequent CD4+ T-cell changes independent of viral load Blood 104,942-947[Abstract/Free Full Text]
  336. 169
  337. Goujard, C., Bonarek, M., Meyer, L., Bonnet, F., Chaix, M. L., Deveau, C., Sinet, M., Galimand, J., Delfraissy, J. F., Venet, A., et al (2006) CD4 cell count and HIV DNA level are independent predictors of disease progression after primary HIV type 1 infection in untreated patients Clin. Infect. Dis. 42,709-715[CrossRef][Medline]
  338. 170
  339. Soudeyns, H., Campi, G., Rizzardi, G. P., Lenge, C., Demarest, J. F., Tambussi, G., Lazzarin, A., Kaufmann, D., Casorati, G., Corey, L., et al (2000) Initiation of antiretroviral therapy during primary HIV-1 infection induces rapid stabilization of the T-cell receptor beta chain repertoire and reduces the level of T-cell oligoclonality Blood 95,1743-1751[Abstract/Free Full Text]
  340. 171
  341. Smith, D. E., Walker, B. D., Cooper, D. A., Rosenberg, E. S., Kaldor, J. M. (2004) Is antiretroviral treatment of primary HIV infection clinically justified on the basis of current evidence? AIDS 18,709-718[CrossRef][Medline]
  342. 172
  343. Lacabaratz-Porret, C., Urrutia, A., Doisne, J. M., Goujard, C., Deveau, C., Dalod, M., Meyer, L., Rouzioux, C., Delfraissy, J. F., Venet, A., Sinet, M. (2003) Impact of antiretroviral therapy and changes in virus load on human immunodeficiency virus (HIV)-specific T cell responses in primary HIV infection J. Infect. Dis. 187,748-757[CrossRef][Medline]
  344. 173
  345. Kaufmann, D. E., Lichterfeld, M., Altfeld, M., Addo, M. M., Johnston, M. N., Lee, P. K., Wagner, B. S., Kalife, E. T., Strick, D., Rosenberg, E. S., et al (2004) Limited durability of viral control following treated acute HIV infection PLoS. Med. 1,137-148
  346. 174
  347. Ghosn, J., Pellegrin, I., Goujard, C., Deveau, C., Viard, J. P., Galimand, J., Harzic, M., Tamalet, C., Meyer, L., Rouzioux, C., et al (2006) HIV-1 resistant strains acquired at the time of primary infection massively fuel the cellular reservoir and persist for lengthy periods of time AIDS 20,159-170[Medline]
  348. 175
  349. Pacanowski, J., Develioglu, L., Kamga, I., Sinet, M., Desvarieux, M., Girard, P. M., Hosmalin, A. (2004) Early plasmacytoid dendritic cell changes predict plasma HIV rebound in primary infection J. Infect. Dis. 190,1889-1892[CrossRef][Medline]
  350. 176
  351. Emilie, D., Burgard, M., Lascoux-Combe, C., Laughlin, M., Krzysiek, R., Pignon, C., Rudent, A., Molina, J. M., Livrozet, J. M., Souala, F., et al (2001) Early control of HIV replication in primary HIV-1 infection treated with antiretroviral drugs and pegylated IFN alpha: results from the Primoferon A (ANRS 086) Study AIDS 15,1435-1437[CrossRef][Medline]
  352. 177
  353. Pope, M., Haase, A. T. (2003) Transmission, acute HIV-1 infection and the quest for strategies to prevent infection Nat. Med. 9,847-852[CrossRef][Medline]
  354. 178
  355. Ashkar, A. A., Yao, X. D., Gill, N., Sajic, D., Patrick, A. J., Rosenthal, K. L. (2004) Toll-like receptor (TLR)-3, but not TLR4, agonist protects against genital herpes infection in the absence of inflammation seen with CpG DNA J. Infect. Dis. 190,1841-1849[CrossRef][Medline]
  356. 179
  357. Diebold, S. S., Kaisho, T., Hemmi, H., Akira, S., Reis e Sousa, C. (2004) Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA Science 303,1529-1531[Abstract/Free Full Text]
  358. 180
  359. Shen, H., Iwasaki, A. (2006) A crucial role for plasmacytoid dendritic cells in antiviral protection by CpG ODN-based vaginal microbicide J Clin Invest 116,2237-43[CrossRef][Medline]
  360. 181
  361. Wang, Y., Abel, K., Lantz, K., Krieg, A. M., McChesney, M. B., Miller, C. J. (2005) The Toll-Like Receptor 7 (TLR7) Agonist, imiquimod, and the TLR9 agonist, CpG ODN, induce antiviral cytokines and chemokines but do not prevent vaginal transmission of simian immunodeficiency virus when applied intravaginally to rhesus macaques J. Virol. 79,14355-14370[Abstract/Free Full Text]
  362. 182
  363. Proietti, E., Bracci, L., Puzelli, S., Di Pucchio, T., Sestili, P., De Vincenzi, E., Venditti, M., Capone, I., Seif, I., De Maeyer, E., et al (2002) Type I IFN as a natural adjuvant for a protective immune response: lessons from the influenza vaccine model J. Immunol. 169,375-383[Abstract/Free Full Text]
  364. 183
  365. Carbonneil, C., Aouba, A., Burgard, M., Cardinaud, S., Rouzioux, C., Langlade-Demoyen, P., Weiss, L. (2003) Dendritic cells generated in the presence of granulocyte-macrophage colony-stimulating factor and IFN-alpha are potent inducers of HIV-specific CD8 T cells AIDS 17,1731-1740[CrossRef][Medline]
  366. 184
  367. Santini, S. M., Lapenta, C., Belardelli, F. (2005) Type I interferons as regulators of the differentiation/activation of human dendritic cells: methods for the evaluation of IFN-induced effects Methods Mol. Med. 116,167-181[Medline]
  368. 185
  369. Teleshova, N., Kenney, J., Williams, V., Van Nest, G., Marshall, J., Lifson, J. D., Sivin, I., Dufour, J., Bohm, R., Gettie, A., et al (2006) CpG-C ISS-ODN activation of blood-derived B cells from healthy and chronic immunodeficiency virus-infected macaques J. Leukoc. Biol. 79,257-267[Abstract/Free Full Text]
  370. 186
  371. Wille-Reece, U., Wu, C. Y., Flynn, B. J., Kedl, R. M., Seder, R. A. (2005) Immunization with HIV-1 Gag protein conjugated to a TLR7/8 agonist results in the generation of HIV-1 Gag-specific Th1 and CD8+ T cell responses J. Immunol. 174,7676-7683[Abstract/Free Full Text]
  372. 187
  373. Jiang, J. Q., Patrick, A., Moss, R. B., Rosenthal, K. L. (2005) CD8+ T-cell-mediated cross-clade protection in the genital tract following intranasal immunization with inactivated human immunodeficiency virus antigen plus CpG oligodeoxynucleotides J. Virol. 79,393-400[Abstract/Free Full Text]
  374. 188
  375. Levy, J. A. (2001) The importance of the innate immune system in controlling HIV infection and disease Trends Immunol. 22,312-316[CrossRef][Medline]
  376. 189
  377. Chougnet, C., Shearer, G. M., Landay, A. L. (2002) The role of antigen-presenting cells in HIV pathogenesis Curr. Infect. Dis. Rep. 4,266-271[Medline]
  378. 190
  379. Kavanagh, D. G., Bhardwaj, N. (2002) A division of labor: DC subsets and HIV receptor diversity Nat. Immunol. 3,891-893[CrossRef][Medline]
  380. 191
  381. Steinman, R. M., Granelli-Piperno, A., Pope, M., Trumpfheller, C., Ignatius, R., Arrode, G., Racz, P., Tenner-Racz, K. (2003) The interaction of immunodeficiency viruses with dendritic cells Curr. Top. Microbiol. Immunol. 276,1-30[Medline]
  382. 192
  383. Stebbing, J., Patterson, S., Gotch, F. (2003) New insights into the immunology and evolution of HIV Cell Res. 13,1-7[CrossRef][Medline]
  384. 193
  385. Collman, R. G., Perno, C. F., Crowe, S. M., Stevenson, M., Montaner, L. J. (2003) HIV and cells of macrophage/dendritic lineage and other non-T cell reservoirs: new answers yield new questions J. Leukoc. Biol. 74,631-634[Abstract/Free Full Text]
  386. 194
  387. Teleshova, N., Frank, I., Pope, M. (2003) Immunodeficiency virus exploitation of dendritic cells in the early steps of infection J. Leukoc. Biol. 74,683-690[Abstract/Free Full Text]
  388. 195
  389. Donaghy, H., Stebbing, J., Patterson, S. (2004) Antigen presentation and the role of dendritic cells in HIV Curr. Opin. Infect. Dis. 17,1-6[CrossRef][Medline]
  390. 196
  391. McKenna, K., Beignon, A. S., Bhardwaj, N. (2005) Plasmacytoid dendritic cells: linking innate and adaptive immunity J. Virol. 79,17-27[Free Full Text]



This article has been cited by other articles:


Home page
BloodHome page
M. Nascimbeni, L. Perie, L. Chorro, S. Diocou, L. Kreitmann, S. Louis, L. Garderet, B. Fabiani, A. Berger, J. Schmitz, et al.
Plasmacytoid dendritic cells accumulate in spleens from chronically HIV-infected patients but barely participate in interferon-{alpha} expression
Blood, June 11, 2009; 113(24): 6112 - 6119.
[Abstract] [Full Text] [PDF]


Home page
J. Leukoc. Biol.Home page
A. Iannello, O. Debbeche, S. Samarani, and A. Ahmad
Antiviral NK cell responses in HIV infection: II. viral strategies for evasion and lessons for immunotherapy and vaccination
J. Leukoc. Biol., July 1, 2008; 84(1): 27 - 49.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
S. Fiorentini, E. Riboldi, F. Facchetti, M. Avolio, M. Fabbri, G. Tosti, P. D. Becker, C. A. Guzman, S. Sozzani, and A. Caruso
HIV-1 matrix protein p17 induces human plasmacytoid dendritic cells to acquire a migratory immature cell phenotype
PNAS, March 11, 2008; 105(10): 3867 - 3872.
[Abstract] [Full Text] [PDF]


Home page
J. Leukoc. Biol.Home page
L. J. Montaner, S. M. Crowe, S. Aquaro, C.-F. Perno, M. Stevenson, and R. G. Collman
Advances in macrophage and dendritic cell biology in HIV-1 infection stress key understudied areas in infection, pathogenesis, and analysis of viral reservoirs
J. Leukoc. Biol., November 1, 2006; 80(5): 961 - 964.
[Abstract] [Full Text] [PDF]


This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jlb.0306154v1
80/5/984    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hosmalin, A.
Right arrow Articles by Lebon, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hosmalin, A.
Right arrow Articles by Lebon, P.