Autophagic modulation during in vivo Trypanosoma cruzi infection, a doublé-edged sword?

A.F. CASASSA; M.C. VANRELL; J.A. CUETO; P.S. ROMANO

Buenos Aires

Congreso; SAIB; 2013

SAIB

AUTOPHAGIC MODULATION DURING IN VIVO Trypanosoma cruzi INFECTION, A DOUBLE-EDGED SWORD Casassa AF, Vanrell MC, Cueto JA, Romano SP. Laboratorio de Biología Celular y Molecular. IHEM-CONICET. FCM. UNC. E-mail: promano@fcm.uncu.edu.ar E-mail: fcasassa@mendoza-conicet.gob.ar Autophagy is a pathway involved in the innate immune response against intracellular pathogens. Beclin-1 (Bcln) is a key protein required for this process. Previously, our group showed that induction of host cell autophagy favors T. cruzi infection in vitro. To evaluate the in vivo effect of autophagy in the infection, we studied mortality, parasitemia and histopathology in autophagy competent Bcln+/+ (WT) and deficient Bcln+/- (KO) mice infected with T. cruzi Y-GFP strain. Additionally, we studied the effect of two autophagy inhibitors, Chloroquine (CQ) and Difluoromethylornithine (DFMO). Our results showed that the infection can be divided in two stages. During the first stage there is a local infection characterized by higher parasitemia at 5 and 7 days post infection (dpi) in WT animals, similarly to the in vitro mechanism. Conversely, the second stage of systemic infection was more aggressive in KO mice, which developed significantly higher parasitemia in subsequent days (10 and 13 dpi). This higher parasitemia was correlated with an earlier death (p=0.002) and a larger number of cardiac amastigotes nests. Interestingly, WT mice treated with both DFMO and CQ evolved similarly to the KO mice. Overall, these results demonstrated that, in contrast to the in vitro effect in non-phagocytic cells, the autophagic process protects against infection by T. cruzi in the in vivo model.