Regulation of dendritic cells intracellular trafficking by SNX17 during antigen cross-presentation

DINAMARCA, S; MAYORGA, LS; CROCE, C; ZALAZAR, A; CEBRIAN, I

Buenos Aires

Congreso; Reunión conjunta de Sociedades de Biociencias; 2017

SAIC-SAIB-SAI-SAA-SAB-SAB-SAFE-SAFIS-SAH-SAP

Cross-presentation by MHC class I molecules allows the detection of exogenous antigens by CD8+ T lymphocytes. This process is crucial to initiate cytotoxic immune responses against many pathogens (i.e. Toxoplasma gondii) and tumors. To achieve efficient cross-presentation, dendritic cells (DCs) have developed highly specialized adaptations of their endocytic network. Consequently, DCs are the most potent antigen presenting cell type to accomplish this immunological process. However, a complete view of the many molecular effectors involved in antigen cross-presentation is still missing. Sorting nexin (SNX) proteins are characterized by the presence of a phox-homology (PX) domain that interacts with elements of the endocytic pathway enriched with phosphatidylinositol-3-monophosphate. In this way, SNXs control key features of endocytosis, as well as endosomal signaling, sorting and tubulation. In this study, we focus on the role of SNX17, which associates with compartments of the early endocytic network and participates in several processes of intracellular recycling. Here, we identify SNX17 as a crucial regulator of antigen cross-presentation by DCs. By silencing the expression of SNX17 with shRNAs, we evaluated in DCs the role of this molecule in the fast and slow recycling pathways by flow cytometry. Furthermore, the knock-down of SNX17 hampered the cross-presentation of soluble, particulate and T. gondii-associated antigens. Our results also demonstrate that SNX17 is actively recruited to the vacuole containing T. gondii parasites in DCs, as observed by immunofluorescence labelling and confocal microscopy analysis. Our findings provide compelling evidence that SNX17 plays a central role in the endocytic trafficking of DCs and is crucial to guarantee an efficient antigen cross-presentation.