Role of MVBs formation during antigen cross-presentation by dendritic cells

IGNACIO CEBRIÁN; LUIS MAYORGA; CRISTINA CROCE

Córdoba

Congreso; SAIB - 52th Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2016

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Dendritic cells (DCs) are key players of the immune system by presenting exogenous antigens in association with MHC-I molecules to induce cytotoxic immune responses against tumors and several pathogens in a process known as cross-presentation. The main goal of our study is to investigate the potential role of multivesicular bodies (MVBs) formation during antigen cross-presentation. To accomplish this, we focus our work on the ESCRT machinery, the best characterized proteins that generate intraluminal vesicles in the endocytic network. Here we show that antigen cross presentation is strongly impaired when DCs were treated with the inhibitor of MVBs formation U18666A. By performing immunofluorescence staining and confocal microscopy, we observed a clear recruitment of the MVBs tetrapanin CD63 and the ESCRT protein CHMP4 to the parasitophorous vacuole (PV) of Toxoplasma gondii after DC infection. Moreover, in the presence of the inhibitor U18666A the recruitment of CD63 to the PV was reduced. Altogether, these results suggest for the first time that MBVs are efficiently recruited to the T. gondii-containing vacuole and that MVBs formation is essential for efficient antigen cross-presentation. Further studies will allow us to understand with better detail the complex interactions that this parasite establishes with the MBVs and the role of the ESCRT machinery in this process.