Yersinia enterocolitica modulates anti-bacterial immune responses by controlling Galectin-1 expression

DAVICINO RC; ELIÇABE, JAVIER; MENDEZ-HUERGO, SANTIAGO; MARÍA S. DI GENARO; GABRIEL A. RABINOVICH

Los Cocos , Córdoba

Otro; FIRST ARGENTINEAN SPRING COURSE IN ADVANCED IMMUNOLOGY; 2013

Socieda Argentina de Inmunología

Yersinia enterocolitica modulates anti-bacterial immune responses by controlling Galectin-1 expression Davicino¹,R; Eliçabe¹,R; Méndez Huergo2,S; Di Genaro¹,S;Rabinovich²,G 1IMIBIO-CONICET, 2IBYME-CONICET Yersinia enterocolitica (Ye) is a Gram-negative enteropathogenic bacteria. The pathogenicity of Ye depends on both chromosome-encoded and virulence plasmid (pYV)-encoded factors that aid bacteria to colonize intestine and to resist the host immune response. Ye inject at least six effector Yersinia outer proteins (Yops). After ingestion, bacteria enter to the Peyer?s patches (PP) and may disseminate to mesenteric lymph nodes (MLN), spleen and liver. Galectin-1 (Gal-1) is a ?proto-type? β-galactoside-binding lectin expressed widely by a variety of cells in immune compartments. As only very little is known about Gal-1 role during bacterial infection, we investigated the expression of endogenous Gal-1 after oral Ye infection and studied its role in the anti-bacterial immune response. C57BL/6 mice expressed Gal-1 at days 5, 7 and 14 after oral infection with Ye. When we compared infected C57BL/6 knockout (Lgals1-/-) with wild-type (WT) mice we found increased weight and survival, lower bacterial load and intestinal histopathological changes in Lgals1-/- mice. Moreover, significantly higher levels of IFN-γ and IL-17 were detected in these mice. Neutralizing cytokine experiments demonstrated the critical role of IFN-γ and IL-17 in Ye clearance in knockout mice. Moreover, treatment of WT mice with anti-Gal-1 IgG or administration of rhGal1 to Lgals1-/- mice confirmed the regulatory role of this lectin during Ye infection. To explore the mechanisms underlying bacterial-induced Gal-1 expression, we infected WT mice with Ye mutants which were deficient in the virulent factor YopP (Ye yopP) or YopH (Ye yopH) and observed a significant decrease in Gal-1 expression and increase in IL-17 production. Moreover, higher level of IL-10 was detected after Ye yopP infection. We conclude that Gal-1 expression induced by bacterial virulence factors plays an immunoregulatory role during Ye infection conferring potential higher pathogenicity and/or host tissue protection during the inflammatory response induced by the bacterial infection.