Endogenous galectin-1 endows dendritic cells with a Th2-polarizing profile during Schistosoma mansoni infection

DERGAN-DYLON S; ILARREGUI JM; RUTITZKY LI; MASCANFRONI I; CERLIANI JP; CROCI DO; TOSCANO MA; SALATINO M; SUNDBLAD V; STADECKER M; RABINOVICH GA

CABA

Congreso; First French-Angentinian Immunology Congress (FAIC); 2010

Sociedad Argentina de Inmunología y Sociedad Francesa de Inmunología

Schistosoma mansoni, a parasite trematode that infects ~83.31 million people worldwide, promotes a CD4 T cell-mediated response and evokes multiple suppressive mechanisms to thwart host immunity. The clinical outcome relies on the ability of the host to transit from an early pro-inflammatory toward a Th2 chronic response. The mechanisms driving this transition are poorly understood. Our laboratory recently identified a tolerogenic circuit linking galectin-1 (Gal1), IL-27 and IL-10 which instructs dendritic cells (DCs) to become tolerogenic. The present study was conducted to examine whether endogenous Gal1 influences Th2-dependent immunity upon stimulation with S. mansoni egg antigen (SEA). Notably, SEA induced a dose-dependent up-regulation of Gal1 on DCs, as shown by Western blot and real time qPCR (p<0.05). Analysis of the cytokine profile of WT and Lgals-1-/- DCs exposed to SEA (DCSEA) revealed no significant differences in IL-23, IL-27 and IL-12p70 secretion, although a statistically-significant decrease was observed in the amounts of IL-10 secreted by Lgals1-/- DCs (p<0.05). To investigate the T-cell stimulatory and polarizing capacity of these cells, we studied the cytokine profile in allogeneic co-cultures composed of WT and Lgals1-/- DCSEA from B6  and splenocytes from WT BALBc mice. DCSEA isolated from WT mice primed T cells to produce higher IL-5 and IL-10 levels (p<0.05) and lower IFN-ã levels (p<0.05) as compared to Lgals1-/- DCSEA.  To study the relevance of these findings in vivo, we assessed the presence of Lgals-1 mRNA by real time qPCR in liver and lymph nodes of CBA and B6 mice, used as models of high and low S. mansoni pathology. We found a dramatic reduction in Lgals1 mRNA (p<0.05) in high pathology CBA as compared to low pathology B6 mice infected with similar doses of this helminth parasite. These results suggest that endogenous Gal-1 plays a key role in S. mansoni -induced TH2 chronic disease by imprinting a DC2-type regulatory signature.