title: Sec22b regulates phagosomal maturation and antigen crosspresentation by dendritic cells.
abstract: Antigen (Ag) crosspresentation by dendritic cells (DCs) involves the presentation of internalized Ags on MHC class I molecules to initiate CD8+ T cell-mediated immunity in response to certain pathogens and tumor cells. Here, we identify the SNARE Sec22b as a specific regulator of Ag crosspresentation. Sec22b localizes to the ER-Golgi intermediate compartment (ERGIC) and pairs to the plasma membrane SNARE syntaxin 4, which is present in phagosomes (Phgs). Depletion of Sec22b inhibits the recruitment of ER-resident proteins to Phgs and to the vacuole containing the Toxoplasma gondii parasite. In Sec22b-deficient DCs, crosspresentation is compromised after Ag phagocytosis or endocytosis and after invasion by T. gondii. Sec22b silencing inhibited Ag export to the cytosol and increased phagosomal degradation by accelerating lysosomal recruitment. Our findings provide insight into an intracellular traffic pathway required for crosspresentation and show that Sec22b-dependent recruitment of ER proteins to Phgs critically influences phagosomal functions in DCs.
authors.affiliation: Institut Curie, INSERM U932, Immunité et Cancer, 26 rue d'Ulm, 75248 Paris Cedex 05, France.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Cebrian
authors.forename: Geraldine
authors.initials: G
authors.lastname: Visentin
authors.forename: Nicolas
authors.initials: N
authors.lastname: Blanchard
authors.forename: Mabel
authors.initials: M
authors.lastname: Jouve
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bobard
authors.forename: Catarina
authors.initials: C
authors.lastname: Moita
authors.forename: Jost
authors.initials: J
authors.lastname: Enninga
authors.forename: Luis F
authors.initials: LF
authors.lastname: Moita
authors.forename: Sebastian
authors.initials: S
authors.lastname: Amigorena
authors.forename: Ariel
authors.initials: A
authors.lastname: Savina
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D003429:Cross Reactions; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010588:Phagosomes / Q000276:immunology*; D050683:R-SNARE Proteins / Q000378:metabolism*; D014122:Toxoplasma; D014123:Toxoplasmosis / Q000276:immunology*
chemical_list: D050683:R-SNARE Proteins; C432415:Sec22b protein, mouse