DM, but not cathepsin L, is required to control an aerosol infection with Mycobacterium tuberculosis

作者：Nepal Rajeev Mani; Vesosky Bridget; Turner Joanne; Bryant Paula^*

来源：Journal of Leukocyte Biology, 2008, 84(4): 1011-1018.

DOI：10.1189/jlb.1207852

• class II MHC
• antigen presentation
• CD4+T cell

Antigen presentation by class II MHC molecules in the uninfected host is a multi-step process involving key functions provided by specific cathepsins (Cat) and the peptide editor DM. Herein, we examined the requirement for each of these components in mice to control a low-dose aerosol infection with Mycobacterium tuberculosis (MTB). Mice lacking Cat B, -L, or -S were similar to wild-type in their ability to control the growth and dissemination of MTB. In contrast, DM(-/-) mice failed to limit MTB growth and showed similar to 100-fold higher bacterial burden in the lung and spleen (5-6 weeks postinfection) as compared with wildtype and Cat-deficient mice. Histopathology revealed impaired cellular recruitment and altered granuloma formation in the lungs of MTB-infected DM(-/-) mice. Moreover, despite impaired thymic selection in Cat L(-/-) and DM(-/-) mice, MTB-specific CD4(+) T cells were elicited only in the former. The lower numbers of MTB-specific CD4(+) T cells available in Cat L(-/-) mice as compared with wildtype animals were sufficient to control MTB growth and dissemination. In addition, DM(-/-) macrophages infected with MTB in vitro were unable to stimulate pathogen-specific T cells. The data indicate that the majority of antigens derived from MTB are loaded onto nascent class II MHC molecules via the classical DM-dependent pathway.

• 出版日期2008-10-1