[HTML][HTML] Apoptosis facilitates antigen presentation to T lymphocytes through MHC-I and CD1 in tuberculosis

UE Schaible, F Winau, PA Sieling, K Fischer… - Nature medicine, 2003 - nature.com
UE Schaible, F Winau, PA Sieling, K Fischer, HL Collins, K Hagens, RL Modlin, V Brinkmann
Nature medicine, 2003nature.com
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 …
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.
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