title: Apoptotic vesicles crossprime CD8 T cells and protect against tuberculosis.
abstract: CD8 T lymphocytes are important effectors in protective immunity against Mycobacterium tuberculosis. We recently characterized the detour pathway of CD8 T cell activation in tuberculosis mediated by apoptotic vesicles from infected cells that transport mycobacterial antigens to dendritic cells (DCs). Here we demonstrate that apoptotic vesicles from mycobacteria-infected macrophages stimulate CD8 T cells in vivo. Homing of DCs to draining lymph nodes was critically required for effective crosspriming. Subsequent fate of vesicle-associated antigens in recipient DCs was characterized by endosomal mechanisms predominating over proteasomal processing. In addition, vesicle processing depended on the presence of saposins to disintegrate apoptotic membranes. Apoptotic vesicles displayed potent adjuvant activity by stimulating through Toll-like receptors (TLR). Ultimately, vaccination with vesicles from infected cells induced protection against M. tuberculosis infection. Taken together, we propose the detour pathway to represent a genuine immunological mechanism mediating crosspriming of CD8 T cells in vivo and protection against tuberculosis.
authors.affiliation: Department of Immunology, Max-Planck-Institute for Infection Biology, Schumannstrasse 21-22, 10117 Berlin, Germany. winau@mpiib-berlin.mpg.de
authors.forename: Florian
authors.initials: F
authors.lastname: Winau
authors.forename: Stephan
authors.initials: S
authors.lastname: Weber
authors.forename: Subash
authors.initials: S
authors.lastname: Sad
authors.forename: Juana
authors.initials: J
authors.lastname: de Diego
authors.forename: Silvia Locatelli
authors.initials: SL
authors.lastname: Hoops
authors.forename: Bernadette
authors.initials: B
authors.lastname: Breiden
authors.forename: Konrad
authors.initials: K
authors.lastname: Sandhoff
authors.forename: Volker
authors.initials: V
authors.lastname: Brinkmann
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
authors.forename: Ulrich E
authors.initials: UE
authors.lastname: Schaible
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis; D001500:BCG Vaccine / Q000276:immunology / Q000627:therapeutic use*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D011992:Endosomes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D008264:Macrophages / Q000382:microbiology / Q000648:ultrastructure; D051379:Mice; D009163:Mycobacterium bovis / Q000276:immunology; D049231:Saposins / Q000378:metabolism; D051193:Toll-Like Receptors / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D014611:Vaccination / Q000379:methods
chemical_list: D000276:Adjuvants, Immunologic; D001500:BCG Vaccine; D049231:Saposins; D051193:Toll-Like Receptors