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

DERGAN DYLON SL; ILARREGUI JM; RUTITZKY L; MASCANFRONI ID; CERLIANI JP; CROCI DO; SALATINO M; TOSCANO MA; SUNDBLAD V; STADECKER M; RABINOVICH GA

Buenos Aires

Congreso; First French-Argentine Immunology Congress; 2010

Sociedad Argentina de Inmunología

Schistosoma mansoni, a parasite trematode that infects 83.3million people worldwide, promotes a CD4 T cell-mediated responseand evokes multiple suppressive mechanisms to thwarthost immunity. The clinical outcome relies on the ability of thehost to transit from an early pro-inflammatory toward a Th2chronic response. The mechanisms driving this transition arepoorly understood. Our laboratory recently identified a tolerogeniccircuit linking galectin-1 (Gal1), IL-27 and IL-10 which instructsdendritic cells (DCs) to become tolerogenic. The presentstudy was conducted to examine whether endogenous Gal1influences Th2-dependent immunity upon stimulation with S.mansoni egg antigen (SEA). Notably, SEA induced a dose-dependentup-regulation of Gal1 on DCs, as shown by westernblot and real time qPCR (p<0.05). Analysis of the cytokine profileof wild type (WT) and Lgals1-/- DCs exposed to SEA (DCSEA) revealedno significant differences in IL-23, IL-27 and IL-12p70 secretion,although a statistically-significant decrease was observedin the amounts of IL-10 secreted by Lgals1-/- DCs (p<0.05). To investigatethe T-cell stimulatory and polarizing capacity of thesecells, we studied the cytokine profile in allogeneic co-culturescomposed of WT and Lgals1-/- DCSEA from B6 and splenocytesfrom WT BALBc mice. DCSEA isolated from WT mice primed Tcells to produce higher IL-5 and IL-10 levels (p<0.05) and lowerIFN-g (p<0.05) levels as compared to Lgals1-/- DCSEA. To studythe relevance of these findings in vivo, we assessed the presenceof Lgals1 mRNA by real time qPCR in liver and lymph nodesof CBA and B6 mice, used as models of high and low S. mansonipathology. We found a dramatic reduction in Lgals1 mRNA(p<0.05) in high pathology CBA as compared to low pathologyB6 mice infected with similar doses of this helminth parasite.These results suggest that endogenous Gal-1 plays a key role inS. mansoni -induced TH2 chronic disease by imprinting a DC2-type regulatory signature.