Nature Medicine9, 1039 - 1046 (2003)
Published online: 20 July 2003; | doi:10.1038/nm906
Apoptosis facilitates antigen presentation to T lymphocytes through MHC-I and CD1 in tuberculosis
Ulrich E Schaible1, Florian Winau1, Peter A Sieling2, Karsten Fischer1, Helen L Collins1, 4, Kristine Hagens1, Robert L Modlin2, Volker Brinkmann3
& Stefan H E Kaufmann1
1
Max-Planck Institute for Infection Biology, Department of Immunology, Schumannstrasse 21-22, D-10117 Berlin, Germany.
2
Division of Dermatology, Department of Microbiology and Immunology and Molecular Biology Institute, University of California Los Angeles School of Medicine, Los Angeles, California 90095, USA.
3
Central Core Facility Microscopy, Max-Planck Institute for Infection Biology, Schumannstrasse 21-22, D-10117 Berlin, Germany.
4
Present address: Division of Life Sciences, Kings College London, Franklin Wilkins Building, 150 Stamford Street, London SE1 9NN, UK.
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.
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