期刊
INFECTION AND IMMUNITY
卷 71, 期 8, 页码 4487-4497出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/IAI.71.8.4487-4497.2003
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资金
- NHLBI NIH HHS [HL55967, R01 HL055967] Funding Source: Medline
- NIAID NIH HHS [R01 AI047255, N01AI95383, R01 AI027243, R01 AI034343, R01 AI035726, AI34343, AI27243, AI35726, AI47255] Funding Source: Medline
Mycobacterium tuberculosis survives in macrophages in the face of acquired CD4(+) T-cell immunity, which controls but does not eliminate the organism. Gamma interferon (IFN-gamma) has a central role in host defenses against M. tuberculosis by activating macrophages and regulating major histocompatibility complex class II (MHC-II) antigen (Ag) processing. M. tuberculosis interferes with IFN-gamma receptor (IFN-gammaR) signaling in macrophages, but the molecules responsible for this inhibition are poorly defined. This study determined that the 19-kDa lipoprotein from M. tuberculosis inhibits IFN-gamma-regulated HLA-DR protein and mRNA expression in human macrophages. Inhibition of HLA-DR expression was associated with decreased processing and presentation of soluble protein Ags and M. tuberculosis bacilli to MHC-II-restricted T cells. Inhibition of HLA-DR required prolonged exposure to 19-kDa lipoprotein and was blocked with a monoclonal antibody specific for Toll-like receptor 2 (TLR-2). The 19-kDa lipoprotein also inhibited IFN-gamma-induced expression of FcgammaRI. Thus, M. tuberculosis, through 19-kDa lipoprotein activation of TLR-2, inhibits IFN-gammaR signaling in human macrophages, resulting in decreased MHC-II Ag processing and recognition by MHC-II-restricted CD4 T cells. These findings provide a mechanism for M. tuberculosis persistence in macrophages.
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