Cross-presentation of antigens from Trypanosoma cruzi

BISCARI, LUCÍA; CAMBRONERA, PAULA; COCORDANO, NABILA; FARRÉ, CECILIA; ALLOATTI, ANDRÉS

Congreso; LXVII Reunión Anual de la Sociedad Argentina de Inmunología; 2019

SAI

Chagas? disease, whose etiological agent is the parasite Trypanosoma cruzi, affects 8 million people worldwide, and cause 15.000 deaths per year. Endemic in Latin America, migration from developing to developed countries also spread the infection to the US and Europe. Current treatments are difficult to administer and present high toxicity. Also, there are no vaccines to prevent or fight the disease. Hence, elucidating the ways by which the anti-parasite immune response is generated will serve to develop novel tools favoring a better infection control. It has been shown that CD8+ T cell responses are of utmost relevance for controlling the infection, but little is known about how these cytotoxic responses are primed.In this work, we use a recently developed mouse line, Sec22bKO, deficient in antigen cross-presentation (but not the classical antigen presentation pathways), to analyze whether such mechanism is of relevance to mount anti-parasite CD8+ T cell responses. We infected Sec22bWT and Sec22bKO mice with tripomastigotes of T. cruzi (strain Y). We analyzed CD8+ T cell responses (global and specific), parasitemia, corporal weight and survival. Sec22bKO mice primed deficient CD8+ T cell responses, either specific for the parasite or general. Additionally, the effector T cell development was affected in Sec22bKO mice. As a consequence, parasitemia was higher and earlier in Sec22bKO, and these mice also lost around 20% of their weight to finally die 30 days after infection, whereas Sec22bWT survived.Hence, cross-presentation is a relevant mechanism contributing to elicit immune responses that will help controlling T. cruzi infection.