SNX27: AN EMERGING MODULATOR OF INTRACELLULAR TRAFFICKING AND ANTIGEN CROSS-PRESENTATION BY DENDRITIC CELLS

SOFÍA DINAMARCA; FACUNDO GARRIDO; NICOLAS BLANCHARD; LUIS S. MAYORGA; IGNACIO CEBRIÁN

San Luis

Congreso; LXXI Reunión Anual de la SAI; 2023

Sociedad Argentina de Inmunología (SAI)

Dendritic cells are remarkable for their ability to uptake exogenous antigens, process and present them on MHC class I molecules to trigger potent cytotoxic immune responses. This process called cross-presentation is critical to counteract the harmful effect of numerous pathogenic microbes and tumor cells. The endocytic pathway of dendritic cells plays a central role for achieving an efficient cross-presentation. In this context, sorting nexin proteins play essential functions in the regulation of several aspects of the endocytic route, such as endocytosis, endosomal sorting, signaling and tubulation. In this work, we focused on the study of SNX27 and its role during intracellular trafficking and antigen cross- presentation by dendritic cells. In particular, SNX27 associates with the retromer complex and mediates the recycling of internalized proteins from endosomes to the plasma membrane. Here, we show that SNX27 silencing results in a defect of both soluble and particulate antigen cross-presentation. Regarding the presentation of the intracellular parasite Toxoplasma gondii, we found that soluble intravacuolar antigens are significantly affected by the knockdown of SNX27 in dendritic cells. However, the parasite immunodominant and transmembrane antigen GRA6 is presented by a different pathway, which isindependent of SNX27 expression. Future and ongoing experiments will help us to elucidate the intracellular steps of cross-presentation governed by SNX27. Our findings provide evidence that SNX27 plays a central role in endocytic trafficking of dendritic cells and is crucial to guarantee an efficient antigen crosspresentation.