Sec22b Regulates Phagosomal Maturation and Antigen Crosspresentation by Dendritic Cells

SummaryAntigen (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.

Graphical AbstractFigure optionsDownload high-quality image (331 K)Download as PowerPoint slideHighlights
► Sec22b mediates the recruitment of ER/ERGIC components to phagosomes
► Crosspresentation of Toxoplasma gondii-associated antigens is Sec22b dependent
► Sec22b is not required for MHC class II and endogenous class I presentation in DCs
► ER/ERGIC-phagosome fusion delays lysosome-phagosome interaction