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.