title: Apoptosis paves the detour path for CD8 T cell activation against intracellular bacteria.
abstract: 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.
authors.affiliation: Max-Planck-Institute for Infection Biology, Department of Immunology, Schumannstr. 21-22, D-10117 Berlin, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Winau
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
authors.forename: Ulrich E
authors.initials: UE
authors.lastname: Schaible
mesh_terms: D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008264:Macrophages / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D012475:Salmonella / Q000276:immunology*; D012480:Salmonella Infections / Q000382:microbiology; D014376:Tuberculosis / Q000382:microbiology