Critical role of endogenous galectin-1 in regulating T helper responses during Yersinia enterocolitica infection

DAVICINO, ROBERTO; ELIçABE, JAVIER; DI GENARO, SILVIA; RABINOVICH, GABRIEL A

Buenos Aires

Congreso; First French - Argentine Immunology Congress. Buenos Aires, Argentina. November 2nd-5th, 2010; 2010

Sociedad Argentina de Inmunologia y Sociedad Francesa de Inmunologia

In spite of considerable advances in elucidating the immunomodulatory functions of galectin-1 in limiting Th1 and Th17 responses in autoimmune settings, the role of this endogenous lectin in microbial infection has not yet been examined. Given that Yersinia enterocolitica, a Gram-negative bacteria evokes Th1-producing IFN-ã immune response, we conducted this study to investigate the absence of endogenous galectin-1 in the development of immunity against this pathogen. We used C57BL/6 wild-type (WT) and Gal-1 knockout (Lgals1-/-) mice which were orogastrically infected with Y. enterocolitica O:8. Survival was compared in both infected mouse groups. On days 5, 14 and 21 after infection, mesenteric lymph nodes (MLN), spleen (Sp) and Peyer's patches (PP) were aseptically obtained, and in their homogenates, colony forming units (CFU) were counted. In addition, we determined concentrations of IL-17 and IFN-ã in PP and serum by ELISA. To elucidate their immunoregulatory effects, spleen cells from Lgals1-/-  mice were adoptively transferred into WT mice; then, these recipient mice were challenged with Y. enterocolitica, and CFU in organs, IL-17 and IFN-ã in PP and serum at 5 days after infection were determined. Higher survival rate was observed in Lgals1-/- compared WT mice (63 % vs 37 %). Furthermore, less CFU in PP after 5 and 14 d after infection of Lgals1-/- mice (p <0.05) and adoptived-transferred WT mice (p<0.05) were determined. At day 21, we did not find CFU in PP, though, we found a decreased counting of CFU on Sp of Lgals1-/- mice (p<0.05). Moreover, higher levels of IFN-ã and IL-17 were detected in sera collected from Lgals1-/- mice and also from adoptive-transferred WT mice (p<0.05). We conclude that the absence of Gal-1 enhances Th1 and Th17 responses which can act to maintain protective immune response favouring eradication of Y. enterocolitica. This is the first report demonstrating a role of endogenous galectin-1 in regulating immunity to infection.