GALECTIN-1 SUBVERTS IMMUNITY BY FOSTERING IMMUNOREGULATORY MECHANISMS DURING A TRYPANOSOMATID INFECTION

PONCINI CV; ILARREGUI JM; BATALLA E; CUCHER MARCELA; VAN KOOYK YVETTE; CERLIANI JP; GONZALEZ CAPPA STELLA M; RABINOVICH GA

Congreso; 4th European Congress of Immunology; 2015

Trypanosoma cruzi is an intracellular protozoan parasite affecting million people in Latin America. During last decade it was increasingly detected in the United States of America, Canada, and many European countries mainly due to population mobility between Latin America and the rest of the world. Experimental infection in mice with virulent T. cruzi strains could be lethal and immunity against the parasite is normally impaired. Dendritic cells (DCs) are essential defining the fate of T cell response. Previously, we have demonstrated that T. cruzi imparts a tolerogenic program in galectin-1 (Gal-1)-sufficient DCs and also that Gal-1 fuels DC-T cell immunoregulatory circuits. Using a model of low dose i.d. infection, we observed early influx of DCs and Gal-1 expression in lymph nodes (LN) draining the site of infection. Gal-1 sufficient mice (WT) developed enhanced susceptibility to infection and enhanced parasite burden in muscle tissues in comparison to Gal-1 deficient (Lgals1-/-) mice. Low number of parasite in Lgals1-/- was accompanied by higher number of CD8+ T cells and IFN-γ producing CD4+ T cells infiltrating cardiac muscle. Moreover in WT, CD4+ T cell response was affected in local LN and differentiation was skewed to non-protective CD4+CD25+FoxP3+ Treg cells. Impairment of Th1-immunity correlated with the tolerogenic properties displayed by Gal-1 sufficient DCs. These results were confirmed in vitro and in vivo by improving the capability of WT mice to control the infection after adoptive transfer of Lgals1-/- DCs. In conclusion, endogenous Gal-1 may tailor T. cruzi infection by fuelling tolerogenic circuits that hinder anti-parasite immune responses.