Apoptosis paves the detour path for CD8 T cell activation against intracellular bacteria.

Winau, F; Kaufmann, SH; Schaible, UE; (2004) Apoptosis paves the detour path for CD8 T cell activation against intracellular bacteria. Cellular microbiology, 6 (7). pp. 599-607. ISSN 1462-5814 DOI: https://doi.org/10.1111/j.1462-5822.2004.00408.x

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Intracellular bacteria such as Mycobacterium tuberculosis primarily infect macrophages. Within these host cells, the pathogens are confined to phagosomes and their antigens are secluded from the classical MHC I presentation pathway. Moreover, macrophages fail to express certain antigen presenting molecules like CD1 proteins. As a result of this intracellular lifestyle, the pathways for the induction of MHC I- and CD1-restricted CD8 T cells by such microorganisms remain elusive. Based on recent findings in tuberculosis and salmonellosis, we propose a new detour pathway for CD8 T cell activation against intracellular bacteria through apoptotic blebs from infected macrophages. Pathogen-derived antigens including proteins and lipids are delivered from infected cells to non-infected dendritic cells. Subsequently, these professional antigen presenting cells display microbial antigens through MHC I and CD1 to T cells. Thus, cross-priming mediated by apoptotic vesicles is not just a matter of antigen distribution, but an intrinsic immunological function due to the nature of phagosomally located intracellular bacteria. We consider infection-induced apoptosis the conditio sine qua non for antigen-specific CD8 T cell activation by phagosome-enclosed pathogens. This important new function of cell death in antibacterial immunity requires consideration for rational vaccine design.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
PubMed ID: 15186397
Web of Science ID: 221853100001
URI: http://researchonline.lshtm.ac.uk/id/eprint/11248


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