Apoptosis facilitates antigen presentation to T lymphocytes through MHC-I and CD1 in tuberculosis |
| |
Authors: | Schaible Ulrich E Winau Florian Sieling Peter A Fischer Karsten Collins Helen L Hagens Kristine Modlin Robert L Brinkmann Volker Kaufmann Stefan H E |
| |
Institution: | Max-Planck Institute for Infection Biology, Department of Immunology, Schumannstrasse 21-22, D-10117 Berlin, Germany. schaible@mpiib-berlin.mpg.de |
| |
Abstract: | Protective immunity against Mycobacterium tuberculosis involves major histocompatibility complex class I (MHC-I)- and CD1-restricted CD8 T cells, but the mechanisms underlying antigen delivery to antigen-presenting molecules remain enigmatic. Macrophages, the primary host cells for mycobacteria, are CD1-negative. Here we show that M. tuberculosis phagosomes are secluded from the cytosolic MHC-I processing pathway and that mycobacteria-infected cells lose their antigen-presenting capacity. We also show that mycobacteria induce apoptosis in macrophages, causing the release of apoptotic vesicles that carry mycobacterial antigens to uninfected antigen-presenting cells (APCs). Inhibition of apoptosis reduced transfer of antigens to bystander cells and activation of CD8 T cells. Uninfected dendritic cells, which engulfed extracellular vesicles, were indispensable for subsequent cross-presentation of antigens, through MHC-I and CD1b, to T cells from mycobacteria-sensitized donors. This new 'detour' pathway for presentation of antigens from a phagosome-contained pathogen shows the functional significance of infection-induced apoptosis in the activation of CD8 T cells specific for both protein and glycolipid antigens in tuberculosis. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|