Published online before print September 2, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
,1
,1,
,2,3
* UMDNJ-New Jersey Medical School,
UMDNJ–Graduate School for Biomedical Sciences, Newark, NJ 07103;
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD 21231; and the
Cancer Institute of New Jersey
3Correspondence: UMDNJ-New Jersey Medical School, Dept. Pathology and Lab. Medicine, 185 So. Orange Ave., Newark, NJ 07103. E-mail: bocarsly{at}umdnj.edu; also, Dr. Paula Pitha, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and The Cancer Research Building, Baltimore, MD 21231. E-mail: parowe{at}jhmi.edu;
Plasmacytoid dendritic cells (PDC) produce high levels of type I IFN upon stimulation with viruses, while monocytes and monocyte-derived dendritic cells (MDDC) produce significantly lower levels. To find what determines the high production of type I IFN in PDC, we examined the relative levels of IRF transcription factors, some of which play critical roles in the induction of IFN. Furthermore, to determine whether the differences could result from expression of distinct IFNA subtypes, the profile of IFNA genes expressed was examined. PDC responded equally well to stimulation with HSV-1 and Sendai virus (SV) by producing high levels of type I IFN, whereas the MDDC and monocyte response to SV were lower, and neither responded well to HSV-1. All three populations constitutively expressed most of the IRF genes. However, real-time RT-PCR demonstrated increased levels of IRF-7 transcripts in PDC compared with monocytes. As determined by intracellular flow cytometry, the PDC constitutively expressed significantly higher levels of IRF-7 protein than the other populations while IRF-3 levels were similar among populations. Analysis of the profile of IFNA genes expressed in virus-stimulated PDC, monocytes and MDDC demonstrated that each population expressed IFNA1 as the major subtype but that the range of the subtypes expressed in PDC was broader, with some donor and stimulus-dependent variability. We conclude that PDC but not MDDC are uniquely preprogrammed to respond rapidly and effectively to a range of viral pathogens with high levels of IFN-
production due to the high levels of constitutively expressed IRF-7.
Key Words: IRF-7 • interferon producing cells • PDC
This article has been cited by other articles:
 |
|
 |
|
  P. Genin, R. Lin, J. Hiscott, and A. Civas Differential Regulation of Human Interferon A Gene Expression by Interferon Regulatory Factors 3 and 7 Mol. Cell. Biol., June 15, 2009; 29(12): 3435 - 3450. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. K. Pfaller and K.-K. Conzelmann Measles Virus V Protein Is a Decoy Substrate for I{kappa}B Kinase {alpha} and Prevents Toll-Like Receptor 7/9-Mediated Interferon Induction J. Virol., December 15, 2008; 82(24): 12365 - 12373. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. D. Nightingale, C. Patkar, and A. L. Rothman Viral replication and paracrine effects result in distinct, functional responses of dendritic cells following infection with dengue 2 virus J. Leukoc. Biol., October 1, 2008; 84(4): 1028 - 1038. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Sachdeva, V. Asthana, T. H. Brewer, D. Garcia, and D. Asthana Impaired Restoration of Plasmacytoid Dendritic Cells in HIV-1-Infected Patients with Poor CD4 T Cell Reconstitution Is Associated with Decrease in Capacity to Produce IFN-{alpha} but Not Proinflammatory Cytokines J. Immunol., August 15, 2008; 181(4): 2887 - 2897. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Tilton, M. M. Manion, M. R. Luskin, A. J. Johnson, A. A. Patamawenu, C. W. Hallahan, N. A. Cogliano-Shutta, J. M. Mican, R. T. Davey Jr., S. Kottilil, et al. Human Immunodeficiency Virus Viremia Induces Plasmacytoid Dendritic Cell Activation In Vivo and Diminished Alpha Interferon Production In Vitro J. Virol., April 15, 2008; 82(8): 3997 - 4006. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Marafioti, J. C. Paterson, E. Ballabio, K. K. Reichard, S. Tedoldi, K. Hollowood, M. Dictor, M.-L. Hansmann, S. A. Pileri, M. J. Dyer, et al. Novel markers of normal and neoplastic human plasmacytoid dendritic cells Blood, April 1, 2008; 111(7): 3778 - 3792. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Herschke, S. Plumet, T. Duhen, O. Azocar, J. Druelle, D. Laine, T. F. Wild, C. Rabourdin-Combe, D. Gerlier, and H. Valentin Cell-Cell Fusion Induced by Measles Virus Amplifies the Type I Interferon Response J. Virol., December 1, 2007; 81(23): 12859 - 12871. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rodriguez-Garcia, H. Oliva, N. Climent, F. Garcia, J. M. Gatell, and T. Gallart Human immature monocyte-derived dendritic cells produce and secrete {alpha}-defensins 1 3 J. Leukoc. Biol., November 1, 2007; 82(5): 1143 - 1146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. A. Jewell, N. Vaghefi, S. E. Mertz, P. Akter, R. S. Peebles Jr., L. O. Bakaletz, R. K. Durbin, E. Flano, and J. E. Durbin Differential Type I Interferon Induction by Respiratory Syncytial Virus and Influenza A Virus In Vivo J. Virol., September 15, 2007; 81(18): 9790 - 9800. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. A. Kittan, A. Bergua, S. Haupt, N. Donhauser, P. Schuster, K. Korn, T. Harrer, and B. Schmidt Impaired Plasmacytoid Dendritic Cell Innate Immune Responses in Patients with Herpes Virus-Associated Acute Retinal Necrosis J. Immunol., September 15, 2007; 179(6): 4219 - 4230. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Bourne, F. Scholle, M. C. Silva, S. L. Rossi, N. Dewsbury, B. Judy, J. B. De Aguiar, M. A. Leon, D. M. Estes, R. Fayzulin, et al. Early Production of Type I Interferon during West Nile Virus Infection: Role for Lymphoid Tissues in IRF3-Independent Interferon Production J. Virol., September 1, 2007; 81(17): 9100 - 9108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhu, X. Huang, and Y. Yang Innate Immune Response to Adenoviral Vectors Is Mediated by both Toll-Like Receptor-Dependent and -Independent Pathways J. Virol., April 1, 2007; 81(7): 3170 - 3180. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. S. C. Graham, H. Manku, S. Wagner, J. Reid, K. Timms, A. Gutin, J. S. Lanchbury, and T. J. Vyse Association of IRF5 in UK SLE families identifies a variant involved in polyadenylation Hum. Mol. Genet., March 15, 2007; 16(6): 579 - 591. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Douagi, G. M. McInerney, A. S. Hidmark, V. Miriallis, K. Johansen, L. Svensson, and G. B. Karlsson Hedestam Role of Interferon Regulatory Factor 3 in Type I Interferon Responses in Rotavirus-Infected Dendritic Cells and Fibroblasts J. Virol., March 15, 2007; 81(6): 2758 - 2768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Cervantes-Barragan, R. Zust, F. Weber, M. Spiegel, K. S. Lang, S. Akira, V. Thiel, and B. Ludewig Control of coronavirus infection through plasmacytoid dendritic-cell-derived type I interferon Blood, February 1, 2007; 109(3): 1131 - 1137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Wang, P. Liu, E. Latz, D. T. Golenbock, R. W. Finberg, and D. H. Libraty Flavivirus Activation of Plasmacytoid Dendritic Cells Delineates Key Elements of TLR7 Signaling beyond Endosomal Recognition J. Immunol., November 15, 2006; 177(10): 7114 - 7121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Fanning, T. C. George, D. Feng, S. B. Feldman, N. J. Megjugorac, A. G. Izaguirre, and P. Fitzgerald-Bocarsly Receptor Cross-Linking on Human Plasmacytoid Dendritic Cells Leads to the Regulation of IFN-{alpha} Production J. Immunol., November 1, 2006; 177(9): 5829 - 5839. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Yount, T. A. Kraus, C. M. Horvath, T. M. Moran, and C. B. Lopez A Novel Role for Viral-Defective Interfering Particles in Enhancing Dendritic Cell Maturation J. Immunol., October 1, 2006; 177(7): 4503 - 4513. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Osawa, S. Iho, R. Takauji, H. Takatsuka, S. Yamamoto, T. Takahashi, S. Horiguchi, Y. Urasaki, T. Matsuki, and S. Fujieda Collaborative Action of NF-{kappa}B and p38 MAPK Is Involved in CpG DNA-Induced IFN-{alpha} and Chemokine Production in Human Plasmacytoid Dendritic Cells J. Immunol., October 1, 2006; 177(7): 4841 - 4852. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Delhaye, S. Paul, G. Blakqori, M. Minet, F. Weber, P. Staeheli, and T. Michiels Neurons produce type I interferon during viral encephalitis PNAS, May 16, 2006; 103(20): 7835 - 7840. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Arimilli, M. A. Alexander-Miller, and G. D. Parks A Simian Virus 5 (SV5) P/V Mutant Is Less Cytopathic than Wild-Type SV5 in Human Dendritic Cells and Is a More Effective Activator of Dendritic Cell Maturation and Function. J. Virol., April 1, 2006; 80(7): 3416 - 3427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ito, H. Kanzler, O. Duramad, W. Cao, and Y.-J. Liu Specialization, kinetics, and repertoire of type 1 interferon responses by human plasmacytoid predendritic cells Blood, March 15, 2006; 107(6): 2423 - 2431. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. O. Kvale, J. Dalgaard, F. Lund-Johansen, H. Rollag, L. Farkas, K. Midtvedt, F. L. Jahnsen, J. E. Brinchmann, and J. Olweus CD11c+ dendritic cells and plasmacytoid DCs are activated by human cytomegalovirus and retain efficient T cell-stimulatory capability upon infection Blood, March 1, 2006; 107(5): 2022 - 2029. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Lehtonen, V. Veckman, T. Nikula, R. Lahesmaa, L. Kinnunen, S. Matikainen, and I. Julkunen Differential Expression of IFN Regulatory Factor 4 Gene in Human Monocyte-Derived Dendritic Cells and Macrophages J. Immunol., November 15, 2005; 175(10): 6570 - 6579. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Bendriss-Vermare, S. Burg, H. Kanzler, L. Chaperot, T. Duhen, O. de Bouteiller, M. D'agostini, J.-M. Bridon, I. Durand, J. M. Sederstrom, et al. Virus overrides the propensity of human CD40L-activated plasmacytoid dendritic cells to produce Th2 mediators through synergistic induction of IFN-{gamma} and Th1 chemokine production J. Leukoc. Biol., October 1, 2005; 78(4): 954 - 966. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Hidmark, G. M. McInerney, E. K. L. Nordstrom, I. Douagi, K. M. Werner, P. Liljestrom, and G. B. K. Hedestam Early Alpha/Beta Interferon Production by Myeloid Dendritic Cells in Response to UV-Inactivated Virus Requires Viral Entry and Interferon Regulatory Factor 3 but Not MyD88 J. Virol., August 15, 2005; 79(16): 10376 - 10385. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Asselin-Paturel and G. Trinchieri Production of type I interferons: plasmacytoid dendritic cells and beyond J. Exp. Med., August 15, 2005; 202(4): 461 - 465. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. M. Hart, V. Athie-Morales, G. M. O'Connor, and C. M. Gardiner TLR7/8-Mediated Activation of Human NK Cells Results in Accessory Cell-Dependent IFN-{gamma} Production J. Immunol., August 1, 2005; 175(3): 1636 - 1642. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Smed-Sorensen, K. Lore, J. Vasudevan, M. K. Louder, J. Andersson, J. R. Mascola, A.-L. Spetz, and R. A. Koup Differential Susceptibility to Human Immunodeficiency Virus Type 1 Infection of Myeloid and Plasmacytoid Dendritic Cells J. Virol., July 15, 2005; 79(14): 8861 - 8869. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Mancl, G. Hu, N. Sangster-Guity, S. L. Olshalsky, K. Hoops, P. Fitzgerald-Bocarsly, P. M. Pitha, K. Pinder, and B. J. Barnes Two Discrete Promoters Regulate the Alternatively Spliced Human Interferon Regulatory Factor-5 Isoforms: MULTIPLE ISOFORMS WITH DISTINCT CELL TYPE-SPECIFIC EXPRESSION, LOCALIZATION, REGULATION, AND FUNCTION J. Biol. Chem., June 3, 2005; 280(22): 21078 - 21090. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Gauzzi, C. Purificato, L. Conti, L. Adorini, F. Belardelli, and S. Gessani IRF-4 expression in the human myeloid lineage: up-regulation during dendritic cell differentiation and inhibition by 1{alpha},25-dihydroxyvitamin D3 J. Leukoc. Biol., June 1, 2005; 77(6): 944 - 947. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Prakash, E. Smith, C.-k. Lee, and D. E. Levy Tissue-specific Positive Feedback Requirements for Production of Type I Interferon following Virus Infection J. Biol. Chem., May 13, 2005; 280(19): 18651 - 18657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Gautier, M. Humbert, F. Deauvieau, M. Scuiller, J. Hiscott, E. E.M. Bates, G. Trinchieri, C. Caux, and P. Garrone A type I interferon autocrine-paracrine loop is involved in Toll-like receptor-induced interleukin-12p70 secretion by dendritic cells J. Exp. Med., May 2, 2005; 201(9): 1435 - 1446. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Abel, Y. Wang, L. Fritts, E. Sanchez, E. Chung, P. Fitzgerald-Bocarsly, A. M. Krieg, and C. J. Miller Deoxycytidyl-Deoxyguanosine Oligonucleotide Classes A, B, and C Induce Distinct Cytokine Gene Expression Patterns in Rhesus Monkey Peripheral Blood Mononuclear Cells and Distinct Alpha Interferon Responses in TLR9-Expressing Rhesus Monkey Plasmacytoid Dendritic Cells Clin. Vaccine Immunol., May 1, 2005; 12(5): 606 - 621. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-K. Conzelmann Transcriptional Activation of Alpha/Beta Interferon Genes: Interference by Nonsegmented Negative-Strand RNA Viruses J. Virol., May 1, 2005; 79(9): 5241 - 5248. [Full Text] [PDF]
|
|
|
|
|
|
J. Schlender, V. Hornung, S. Finke, M. Gunthner-Biller, S. Marozin, K. Brzozka, S. Moghim, S. Endres, G. Hartmann, and K.-K. Conzelmann Inhibition of Toll-Like Receptor 7- and 9-Mediated Alpha/Beta Interferon Production in Human Plasmacytoid Dendritic Cells by Respiratory Syncytial Virus and Measles Virus J. Virol., May 1, 2005; 79(9): 5507 - 5515. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Schoenemeyer, B. J. Barnes, Margo. E. Mancl, E. Latz, N. Goutagny, P. M. Pitha, K. A. Fitzgerald, and D. T. Golenbock The Interferon Regulatory Factor, IRF5, Is a Central Mediator of Toll-like Receptor 7 Signaling J. Biol. Chem., April 29, 2005; 280(17): 17005 - 17012. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Chung, S. B. Amrute, K. Abel, G. Gupta, Y. Wang, C. J. Miller, and P. Fitzgerald-Bocarsly Characterization of Virus-Responsive Plasmacytoid Dendritic Cells in the Rhesus Macaque Clin. Vaccine Immunol., March 1, 2005; 12(3): 426 - 435. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Stewart, K. Smoak, M. A. Blum, and B. Sherry Basal and Reovirus-Induced Beta Interferon (IFN-{beta}) and IFN-{beta}-Stimulated Gene Expression Are Cell Type Specific in the Cardiac Protective Response J. Virol., March 1, 2005; 79(5): 2979 - 2987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Tamura, P. Tailor, K. Yamaoka, H. J. Kong, H. Tsujimura, J. J. O'Shea, H. Singh, and K. Ozato IFN Regulatory Factor-4 and -8 Govern Dendritic Cell Subset Development and Their Functional Diversity J. Immunol., March 1, 2005; 174(5): 2573 - 2581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. McKenna, A.-S. Beignon, and N. Bhardwaj Plasmacytoid Dendritic Cells: Linking Innate and Adaptive Immunity J. Virol., January 1, 2005; 79(1): 17 - 27. [Full Text] [PDF]
|
|
|
|
|
|
B. J. Barnes, J. Richards, M. Mancl, S. Hanash, L. Beretta, and P. M. Pitha Global and Distinct Targets of IRF-5 and IRF-7 during Innate Response to Viral Infection J. Biol. Chem., October 22, 2004; 279(43): 45194 - 45207. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Dai, N. J. Megjugorac, S. B. Amrute, and P. Fitzgerald-Bocarsly Regulation of IFN Regulatory Factor-7 and IFN-{alpha} Production by Enveloped Virus and Lipopolysaccharide in Human Plasmacytoid Dendritic Cells J. Immunol., August 1, 2004; 173(3): 1535 - 1548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Lubyova, M. J. Kellum, A. J. Frisancho, and P. M. Pitha Kaposi's Sarcoma-associated Herpesvirus-encoded vIRF-3 Stimulates the Transcriptional Activity of Cellular IRF-3 and IRF-7 J. Biol. Chem., February 27, 2004; 279(9): 7643 - 7654. [Abstract] [Full Text] [PDF]
|
|
