DO GALECTIN-GLYCAN INTERACTIONS PLAY ANY ROLE IN LINKING COMMENSAL MICROBIOTA, T CELLS AND THE INTESTINAL EPITHELIUM?

MOROSI L; CUTINE A; MORALES RM; BLANCATO VS; MAGNI C; DE MENDOZA D; TOSCANO MA; RABINOVICH GA; MARIÑO KV

Mar del Plata

Congreso; LXII REUNIÓN ANUAL Sociedad Argentina de Inmunología; 2014

The intestinal microbiota plays a crucial role in the host defense, helping to shape the immune system throughout life. A dynamic dialogue between intestinal immune cells and bacteria ensures a homeostatic immune state, which includes protection from pathogens and hypo-responsiveness to environmental antigens (dietary antigens and commensals). The mechanisms underlying this delicate balance are not completely understood. Galectins, soluble lectins capable of recognizing N-acetyllactosamine residues in glycoconjugates, are key modulators of the immune response. Galectin-1 (Gal1), a member of this family, can directly induce apoptosis of TH1 and TH17 lymphocytes or activate regulatory circuits mediated by T regulatory cells (Tregs) and regulatory dendritic cells. However, little is known on the influence of microbiota on the intestinal repertoire of galectins and on the glycophenotype of epithelial and mucosa-associated immune cells. We studied the effects of oral daily administration of Lactococcus lactis NZ9000, Lactobacillus casei BL23 and Enteroccocus faecalis JH2-2 (commensal bacteria) to 8 weeks-old male BALB/c mice. Using flow cytometry, we characterized the glycophenotype of intestinal epithelia and CD4 and CD8 T cells isolated both from spleen (systemic) and subepithelial cells/lamina propria (local compartment). The galectin gene expression profile was also analyzed by RT-qPCR. Our results showed that the glycophenotype of T cells (CD4 or CD8) is different between subepithelial and lamina propria. Moreover, in the presence of commensal bacteria, CD4 and CD8 T cells developed a differential glycophenotype in the local compartment (but not at the systemic level), both when compared to controls and between T cell populations. Colonization by commensal bacteria also caused a three-fold downregulation of Gal1 expression in epithelial and lamina propria compartments, showing that galectin-glycan interactions could be involved in intestinal tolerance to microbiota.