Inhibition of major histocompatibility complex II expression and antigen processing in murine alveolar macrophages by Mycobacterium bovis BCG and the 19-kilodalton mycobacterial lipoprotein.
Alveolar macrophages constitute a primary defense against Mycobacterium tuberculosis, but they are unable to control M. tuberculosis without acquired T-cell immunity. This study determined the antigen-presenting cell function of murine alveolar macrophages and the ability of the model mycobacterium, Mycobacterium bovis BCG, to modulate it. The majority (80 to 85%) of alveolar macrophages expressed both CD80 (B7.1) and CD11c, and 20 to 30% coexpressed major histocompatibility complex II (MHC-II). Gamma interferon (IFN-gamma) enhanced MHC-II but not B7.1 expression. Naive or IFN-gamma-treated alveolar macrophages did not express CD86 (B7.2), CD11b, Mac-3, CD40, or F4/80. M. bovis BCG and the 19-kDa mycobacterial lipoprotein inhibited IFN-gamma-regulated MHC-II expression on alveolar macrophages, and inhibition was dependent on Toll-like receptor 2. The inhibition of MHC-II expression by the 19-kDa lipoprotein was associated with decreased presentation of soluble antigen to T cells. Thus, susceptibility to tuberculosis may result from the ability of mycobacteria to interfere with MHC-II expression and antigen presentation by alveolar macrophages.
Fulton
Scott A
SA
Division of Infectious Diseases. Institute of Pathology, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio 44106-4984.
Reba
Scott M
SM
Pai
Rish K
RK
Pennini
Meghan
M
Torres
Martha
M
Harding
Clifford V
CV
Boom
W Henry
WH
D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology*; D018122:B7-1 Antigen / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D008074:Lipoproteins / Q000276:immunology* / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology
D018122:B7-1 Antigen; D039521:CD11c Antigen; D000949:Histocompatibility Antigens Class II; D008074:Lipoproteins; D007371:Interferon-gamma