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Toll-Like Receptor 2-Dependent Inhibition of Macrophage Class II MHC Expression and Antigen Processing by 19-kDa Lipoprotein of Mycobacterium tuberculosis

Erika H. Noss, Rish K. Pai, Timothy J. Sellati, Justin D. Radolf, John Belisle, Douglas T. Golenbock, W. Henry Boom and Clifford V. Harding
J Immunol July 15, 2001, 167 (2) 910-918; DOI: https://doi.org/10.4049/jimmunol.167.2.910
Erika H. Noss
*Department of Pathology,
†Division of Infectious Diseases, and
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Rish K. Pai
*Department of Pathology,
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Timothy J. Sellati
§Center for Microbial Pathogenesis, University of Connecticut Health Center, Farmington, CT 06030;
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Justin D. Radolf
§Center for Microbial Pathogenesis, University of Connecticut Health Center, Farmington, CT 06030;
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John Belisle
¶Department of Microbiology, Colorado State University, Fort Collins, CO 80523; and
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Douglas T. Golenbock
∥Maxwell Finland Laboratory for Infectious Diseases, Boston Medical Center, Boston, MA 02118
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W. Henry Boom
†Division of Infectious Diseases, and
‡Tuberculosis Research Unit, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH, 44106;
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Clifford V. Harding
*Department of Pathology,
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Abstract

Mycobacterium tuberculosis (MTB) induces vigorous immune responses, yet persists inside macrophages, evading host immunity. MTB bacilli or lysate was found to inhibit macrophage expression of class II MHC (MHC-II) molecules and MHC-II Ag processing. This report characterizes and identifies a specific component of MTB that mediates these inhibitory effects. The inhibitor was extracted from MTB lysate with Triton X-114, isolated by gel electroelution, and identified with Abs to be MTB 19-kDa lipoprotein. Electroelution- or immunoaffinity-purified MTB 19-kDa lipoprotein inhibited MHC-II expression and processing of both soluble Ags and Ag 85B from intact MTB bacilli. Inhibition of MHC-II Ag processing by either MTB bacilli or purified MTB 19-kDa lipoprotein was dependent on Toll-like receptor (TLR) 2 and independent of TLR 4. Synthetic analogs of lipopeptides from Treponema pallidum also inhibited Ag processing. Despite the ability of MTB 19-kDa lipoprotein to activate microbicidal and innate immune functions early in infection, TLR 2-dependent inhibition of MHC-II expression and Ag processing by MTB 19-kDa lipoprotein during later phases of macrophage infection may prevent presentation of MTB Ags and decrease recognition by T cells. This mechanism may allow intracellular MTB to evade immune surveillance and maintain chronic infection.

  • Received February 8, 2001.
  • Accepted May 3, 2001.
  • Copyright © 2001 by The American Association of Immunologists
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The Journal of Immunology: 167 (2)
The Journal of Immunology
Vol. 167, Issue 2
15 Jul 2001
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Toll-Like Receptor 2-Dependent Inhibition of Macrophage Class II MHC Expression and Antigen Processing by 19-kDa Lipoprotein of Mycobacterium tuberculosis
Erika H. Noss, Rish K. Pai, Timothy J. Sellati, Justin D. Radolf, John Belisle, Douglas T. Golenbock, W. Henry Boom, Clifford V. Harding
The Journal of Immunology July 15, 2001, 167 (2) 910-918; DOI: 10.4049/jimmunol.167.2.910

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Toll-Like Receptor 2-Dependent Inhibition of Macrophage Class II MHC Expression and Antigen Processing by 19-kDa Lipoprotein of Mycobacterium tuberculosis
Erika H. Noss, Rish K. Pai, Timothy J. Sellati, Justin D. Radolf, John Belisle, Douglas T. Golenbock, W. Henry Boom, Clifford V. Harding
The Journal of Immunology July 15, 2001, 167 (2) 910-918; DOI: 10.4049/jimmunol.167.2.910
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