PERSONAL DE APOYO
BATALLA Estela
congresos y reuniones científicas
Título:
Critical role of endogenous galectin-1 in shaping dendritic cells tolerogenicity by the protozoan parasite Trypanosoma cruzi
Autor/es:
PONCINI C; ILARREGUI JM; BATALLA, E; CUCHER MA; RABINOVICH GA; GONZÁLEZ CAPPA SM
Lugar:
francia
Reunión:
Simposio; 13th Symposium on Dendritic Cells, Tours-Francia, 2014; 2014
Resumen:
Trypanosoma cruzi, the etiological agent of Chagas? disease, is an intracellular protozoan parasite that affects millions of people in Latin America. Despite several decades of research, immunological mechanisms underlying this silent infection and the progression of heart pathology remain elusive. Subverting immunity is a common strategy displayed by pathogens that settle chronic infections. Using in vitro strategies we have previously demonstrated that bone marrow-derived dendritic cells (DCs) stimulated with trypomastigotes (Tp, circulating stage) display tolerogenic properties. Galectins are conserved glycan-binding proteins with multiple roles in the regulation of innate and adaptive immunity. Previous studies demonstrated that DCs differentiated or matured in a galectin-1 (Gal-1)-enriched microenvironment acquire a distinctive ?regulatory signature?. Otherwise, the lack of Gal-1 enhances DCs immunogenicity. Based on this background, we studied the role of endogenous Gal1 during T. cruzi experimental infection in susceptible C57BL/6 mice. We found incremented the expression of Gal-1 in the spleen of infected mice and the lack of Gal-1 conferred resistance to T. cruzi; Lgals1-/- mice displayed delayed mortality, accompanied by less skeletal and cardiac muscle parasitism compared to their wildtype (WT) counterpart. Consistently, WT-infected mice presented expansion of the myeloid compartment in the spleen with enhanced number of DCs with tolerogenic properties analysed ex vivo, and high frequency of CD4+Foxp3+ Treg cells at day 9 post-infection. In addition, these mice displayed less CD8+ T cells in muscle tissues than Gal1-deficient counterpart. All together, these results suggest that endogenous Gal-1 fosters immunosuppressive mechanisms early during parasite-spreading, affecting immunity and favoring T. cruzi persistence in host tissues. Results obtained in vitro confirmed the relevance of parasiteconditioned tolerogenic DCs in mediating the induction of suppressive CD4+Foxp3+ Treg cells, via Gal-1-dependent mechanism. For the first time, our study identifies a critical role for Gal-1 in subverting anti-parasite responses during the acute phase of T. cruzi Infection.