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

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kincaid, E. Z. Articles by Ernst, J. D. Search for Related Content PubMed PubMed Citation Articles by Kincaid, E. Z. Articles by Ernst, J. D. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH

Codominance of TLR2-Dependent and TLR2-Independent Modulation of MHC Class II in Mycobacterium tuberculosis Infection In Vivo¹

Eleanor Z. Kincaid^*,, Andrea J. Wolf^*,, Ludovic Desvignes^*, Sebabrata Mahapatra, Dean C. Crick, Patrick J. Brennan, Martin S. Pavelka, Jr. and Joel D. Ernst^2,*,,¶,||

^* Division of Infectious Diseases, Department of Medicine, New York University School of Medicine, New York, NY 10016; Biomedical Sciences Graduate Program, University of California, San Francisco, CA 94143; Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523; Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14642; and Departments of ^¶ Pathology and ^|| Microbiology, New York University School of Medicine, New York, NY 10016

Mycobacterium tuberculosis is an exceptionally successful human pathogen. A major component of this success is the ability of the bacteria to infect immunocompetent individuals and to evade eradication by an adaptive immune response that includes production of the macrophage-activating cytokine, IFN-. Although IFN- is essential for arrest of progressive tuberculosis, it is insufficient for efficacious macrophage killing of the bacteria, which may be due to the ability of M. tuberculosis to inhibit selected macrophage responses to IFN-. In vitro studies have determined that mycobacterial lipoproteins and other components of the M. tuberculosis cell envelope, acting as agonists for TLR2, inhibit IFN- induction of MHC class II. In addition, M. tuberculosis peptidoglycan and IL-6 secreted by infected macrophages inhibit IFN- induction of MHC class II in a TLR2-independent manner. To determine whether TLR2-dependent inhibition of macrophage responses to IFN- is quantitatively dominant over the TLR2-independent mechanisms in vivo, we prepared mixed bone marrow chimeric mice in which the hemopoietic compartment was reconstituted with a mixture of TLR^+/+ and TLR2^–/– cells. When the chimeric mice were infected with M. tuberculosis, the expression of MHC class II on TLR2^+/+ and TLR2^–/– macrophages from the lungs of individual infected chimeric mice was indistinguishable. These results indicate that TLR2-dependent and -independent mechanisms of inhibition of responses to IFN- are equivalent in vivo, and that M. tuberculosis uses multiple pathways to abrogate the action of an important effector of adaptive immunity.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants AI046097, AI051242, AI059667 (to J.D.E.), AI47311 (to M.S.P.), AI065357-020010, AI049151 (to D.C.C.), and AI018357 (to P.J.B.); a grant from the College Research Council, College of Veterinary Medicine and Biomedical Sciences, Colorado State University; and a graduate student fellowship from the Western Affiliate of the American Heart Association (to E.Z.K.).

² Address correspondence and reprint requests to Dr. Joel D. Ernst, New York University School of Medicine, Smilow Research Center, Room 901, 550 First Avenue, New York, NY 10016. E-mail address: joel.ernst{at}med.nyu.edu

³ Abbreviations used in this paper: DC, dendritic cell; BMDM, bone marrow-derived macrophage.

This article has been cited by other articles:

				M. Gonzalez-Juarrero, L. C. Kingry, D. J. Ordway, M. Henao-Tamayo, M. Harton, R. J. Basaraba, W. H. Hanneman, I. M. Orme, and R. A. Slayden Immune Response to Mycobacterium tuberculosis and Identification of Molecular Markers of Disease Am. J. Respir. Cell Mol. Biol., April 1, 2009; 40(4): 398 - 409. [Abstract] [Full Text] [PDF]

				A. YOSHIDA, H. INAGAWA, C. KOHCHI, T. NISHIZAWA, and G.-I. SOMA The Role of Toll-like Receptor 2 in Survival Strategies of Mycobacterium tuberculosis in Macrophage Phagosomes Anticancer Res, March 1, 2009; 29(3): 907 - 910. [Abstract] [Full Text] [PDF]

				M. Skold and S. M. Behar Tuberculosis Triggers a Tissue-Dependent Program of Differentiation and Acquisition of Effector Functions by Circulating Monocytes J. Immunol., November 1, 2008; 181(9): 6349 - 6360. [Abstract] [Full Text] [PDF]