Abstract

Event Abstract Back to Event An essential role of galectin-1 in driving Th2-polarized responses during helminth infection Leonardo S. Dergan Dylon1*, Juan Ilarregui1, Laura Rutitzky2, Miguel Stadecker2 and Gabriel A. Rabinovich1 1 Instituto de Biología y Medicina Experimental, Argentina 2 Tufts University, Department of Pathology, United States Schistosomiasis, a disease caused by Schistosoma mansoni, affects approximately 238 million people in tropical and sub-tropical areas. Despite considerable efforts in elucidating the mechanisms underlying immune protection and evasion during S. mansoni infection, the endogenous mediators responsible of driving Th2-polarized reactions remain uncertain. Here we identified a crucial role for galectin-1 (Gal-1) an endogenous glycan-binding protein, in driving Th2 responses during S. mansoni infection. Schistosome Egg Antigen (SEA) induced a dose-dependent up-regulation of Gal-1 in bone marrow-derived dendritic cells (DCs), as shown by western blot, real time qPCR and ELISA (p<0.05). Analysis of the cytokine profile of wild type (WT) and Gal-1-deficient (Lgals1-/-) DCs exposed to SEA (DCSEA) revealed no significant differences in IL-23, IL-27, IL-10 and IL-12p70 secretion. In contrast, Lgals1-/- DCs showed lower IL-5 and IL-10 (p<0.05) and higher production of IFN-γ (p<0.05) than WT DCSEA in allogeneic co-cultures using Balb/c splenocytes. An in vivo infection model confirmed our findings showing that, compared to their WT counterpart, splenic DCs isolated from Lgals1-/- infected mice induced allogeneic T cells to produce lower amounts of IL-5 and IL-10 (p<0.01) and higher IFN-γ (p<0.01). This effect correlated with an increased Th2 response observed in T cells isolated from WT lymph nodes (LN) and spleen (p<0.05). Likewise Lgals1-/- infected mice displayed smaller size of granulomas and WT granulomas expressed higher amounts of Gal-1 as shown by qRT-PCR an IHC. These results show a pivotal role for Gal-1 in driving Th2 responses during helminths infection.

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