HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print August 30, 2006

This Article Full Text (Reprint (PDF)) All Versions of this Article: jlb.0306206v1 80/5/1136    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vázquez, N. Articles by Wahl, S. M. Search for Related Content PubMed PubMed Citation Articles by Vázquez, N. Articles by Wahl, S. M.

© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0306206

Received for publication March 15, 2006.
Revised June 2, 2006.
Accepted for publication June 5, 2006.

Article

Mycobacterium avium-induced SOCS contributes to resistance to IFN--mediated mycobactericidal activity in human macrophages

Nancy Vázquez ^*@, Teresa Greenwell-Wild ^*, Sofia Rekka ^*, Jan M. Orenstein , and Sharon M. Wahl ^*

*Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland; and Department of Pathology, George Washington University, Washington, DC

^@ To whom correspondence should be addressed. E-mail: nvazquez{at}mail.nih.gov.

	Abstract

Mycobacterium avium is an opportunistic pathogen that commonly infects individuals colonized with HIV-1, although it is less frequent in the post-HAART era. These microorganisms invade macrophages after interacting with TLR2 and/or CD14 co-receptors, but signaling pathways promoting survival in macrophages are not well defined. Although IFN- plays an important role in protective immunity against bacterial infections, IFN- responses are compromised in AIDS patients and evidence suggests that exogenous IFN- is inadequate to clear the mycobacteria. To determine the mechanism by which M. avium survives intracellularly, even in the presence of IFN-, we studied the effect of mycobacteria infection in macrophages during early IFN- signaling events. M. avium infected cells exhibited a reduced response to IFN-, with suppressed phosphorylation of STAT-1 compared with uninfected cells. Interaction of M. avium with macrophage receptors increased gene expression of the suppressors of cytokine signaling (SOCS) to diminish IFN responsiveness. Specifically, we observed an increase in mRNA for both SOCS-3 and SOCS-1, which correlates with elevated levels of SOCS protein and positive immunostaining in M. avium/HIV-1 co-infected tissues. We also linked the p38 MAPK signaling pathway to mycobacterial-induced SOCS gene transcription. The induction of SOCS may be part of the strategy that allows the invader to render the macrophages unresponsive to IFN-, which otherwise promotes clearance of the infection. Our data provide new insights into the manipulation of the host response by this opportunistic pathogen and the potential for modulating SOCS to influence the outcome of M. avium infection in immunocompromised hosts.

Key Words: AIDS • STAT • HIV

This article has been cited by other articles:

				N. Gratz, M. Siller, B. Schaljo, Z. A. Pirzada, I. Gattermeier, I. Vojtek, C. J. Kirschning, H. Wagner, S. Akira, E. Charpentier, et al. Group A Streptococcus Activates Type I Interferon Production and MyD88-dependent Signaling without Involvement of TLR2, TLR4, and TLR9 J. Biol. Chem., July 18, 2008; 283(29): 19879 - 19887. [Abstract] [Full Text] [PDF]

				Y. Narayana and K. N. Balaji NOTCH1 Up-regulation and Signaling Involved in Mycobacterium bovis BCG-induced SOCS3 Expression in Macrophages J. Biol. Chem., May 2, 2008; 283(18): 12501 - 12511. [Abstract] [Full Text] [PDF]

				T. Yang, P. Stark, K. Janik, H. Wigzell, and M. E. Rottenberg SOCS-1 Protects against Chlamydia pneumoniae-Induced Lethal Inflammation but Hampers Effective Bacterial Clearance J. Immunol., March 15, 2008; 180(6): 4040 - 4049. [Abstract] [Full Text] [PDF]

				H. Qin, K. L. Roberts, S. A. Niyongere, Y. Cong, C. O. Elson, and E. N. Benveniste Molecular Mechanism of Lipopolysaccharide-Induced SOCS-3 Gene Expression in Macrophages and Microglia J. Immunol., November 1, 2007; 179(9): 5966 - 5976. [Abstract] [Full Text] [PDF]

				J. Humann, R. Bjordahl, K. Andreasen, and L. L. Lenz Expression of the p60 Autolysin Enhances NK Cell Activation and Is Required for Listeria monocytogenes Expansion in IFN-{gamma}-Responsive Mice J. Immunol., February 15, 2007; 178(4): 2407 - 2414. [Abstract] [Full Text] [PDF]

				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]