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1
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Division of Rheumatology and Immunology, Department of Internal Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston MA 02115; and
Pulmonary Center, Boston University School of Medicine, Boston, MA 02118
Infection by Mycobacterium tuberculosis (MTB)
induces human alveolar macrophage (AM
) apoptosis by a
TNF-
-dependent mechanism. The apoptotic response is postulated to be
a defense mechanism, limiting the growth of this intracellular
pathogen. Consistent with that model, recent studies showed that the
virulent MTB strain H37Rv induces substantially less AM apoptosis
than the attenuated strain H37Ra. We now report that AM infection
with either H37Rv or H37Ra induces comparable levels of TNF-
measured by ELISA but that TNF- bioactivity is reduced in
supernatants of H37Rv-infected AM. Differential release of soluble
TNFR2 (sTNFR2), with formation of inactive TNF--TNFR2 complexes
accounted for the difference in TNF- bioactivity in these cultures.
Release of sTNFR2 by H37Rv-infected AM was IL-10 dependent since it
was inhibited by neutralizing anti-IL-10 Ab. Thus, the effect of
TNF- produced by AM following infection can be modulated by
virulent MTB, using IL-10 as an upstream
mediator.
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V. P. Mohan, C. A. Scanga, K. Yu, H. M. Scott, K. E. Tanaka, E. Tsang, M. C. Tsai, J. L. Flynn, and J. Chan Effects of Tumor Necrosis Factor Alpha on Host Immune Response in Chronic Persistent Tuberculosis: Possible Role for Limiting Pathology Infect. Immun., March 1, 2001; 69(3): 1847 - 1855. [Abstract] [Full Text] [PDF]
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J. E. Wigginton and D. Kirschner A Model to Predict Cell-Mediated Immune Regulatory Mechanisms During Human Infection with Mycobacterium tuberculosis J. Immunol., February 1, 2001; 166(3): 1951 - 1967. [Abstract] [Full Text] [PDF]
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D. Fortsch, M. Rollinghoff, and S. Stenger IL-10 Converts Human Dendritic Cells into Macrophage-Like Cells with Increased Antibacterial Activity Against Virulent Mycobacterium tuberculosis J. Immunol., July 15, 2000; 165(2): 978 - 987. [Abstract] [Full Text] [PDF]
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 M. Behnia, K. A. Robertson, and W. J. Martin II Lung Infections : Role of Apoptosis in Host Defense and Pathogenesis of Disease Chest, June 1, 2000; 117(6): 1771 - 1777. [Abstract] [Full Text] [PDF]
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Y. Geng, R. B. Shane, K. Berencsi, E. Gonczol, M. H. Zaki, D. J. Margolis, G. Trinchieri, and A. H. Rook Chlamydia pneumoniae Inhibits Apoptosis in Human Peripheral Blood Mononuclear Cells Through Induction of IL-10 J. Immunol., May 15, 2000; 164(10): 5522 - 5529. [Abstract] [Full Text] [PDF]
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J. Keane, H. G. Remold, and H. Kornfeld Virulent Mycobacterium tuberculosis Strains Evade Apoptosis of Infected Alveolar Macrophages J. Immunol., February 15, 2000; 164(4): 2016 - 2020. [Abstract] [Full Text] [PDF]
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D. J. Kusner and J. Adams ATP-Induced Killing of Virulent Mycobacterium tuberculosis Within Human Macrophages Requires Phospholipase D J. Immunol., January 1, 2000; 164(1): 379 - 388. [Abstract] [Full Text] [PDF]
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M. Rojas, M. Olivier, P. Gros, L. F. Barrera, and L. F. Garcia TNF-{alpha} and IL-10 Modulate the Induction of Apoptosis by Virulent Mycobacterium tuberculosis in Murine Macrophages J. Immunol., May 15, 1999; 162(10): 6122 - 6131. [Abstract] [Full Text] [PDF]
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