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Infection and Immunity, April 2004, p. 2101-2110, Vol. 72, No. 4
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.4.2101-2110.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Inhibition of Major Histocompatibility Complex II Expression and Antigen Processing in Murine Alveolar Macrophages by Mycobacterium bovis BCG and the 19-Kilodalton Mycobacterial Lipoprotein

Scott A. Fulton,1 Scott M. Reba,1 Rish K. Pai,2 Meghan Pennini,2 Martha Torres,1,{dagger} Clifford V. Harding,2 and W. Henry Boom1*

Division of Infectious Diseases,1 Institute of Pathology, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio 44106-49842

Received 1 October 2003/ Returned for modification 12 November 2003/ Accepted 8 January 2004

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.

* Corresponding author. Mailing address: Division of Infectious Diseases, Biomedical Research Building, Room 1031, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106-4984. Phone: (216) 368-4847. Fax: (216) 368-2034. E-mail: whb{at}po.cwru.edu.

Editor: F. C. Fang

{dagger} Present address: Departamento de Microbiologia, Instituto Nacional de Enfermedades Respiratorias, Tlalpan 14080, Mexico City, Mexico.

Infection and Immunity, April 2004, p. 2101-2110, Vol. 72, No. 4
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.4.2101-2110.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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