IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Galectin-glycan interactions at the crossroads between commensal microbiota and T cell function
Autor/es:
LUCIANO G. MOROSI; ANABELA M. CUTINE; ROSA M. MORALES; VÍCTOR S. BLANCATO; CHRISTIAN MAGNI; DIEGO DE MENDOZA; MARTA A. TOSCANO; GABRIEL A. RABINOVICH; KARINA MARIÑO
Lugar:
Paris
Reunión:
Congreso; 2nd World Congress on Targeting Microbiota - Towards Clinical Revolution; 2014
Institución organizadora:
Institut Pasteur
Resumen:
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 not only protection from pathogens but also hypo-responsiveness to environmental antigens (dietary and/or commensal antigens). 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. There is solid evidence of their essential yet diverse roles in immunoregulation, mediated by their interaction with glycoconjugates on the cellular surface: 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. Galectin-3 (Gal3), on the other hand, is implicated in a variety of biological processes including host−pathogen interactions and microbicidal activity. However, little is known on how commensal microbiota affects the intestinal repertoire of galectins and the glycophenotype (exposed cell surface glycans) 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 to 8 weeks-old male BALB/c mice. Using flow cytometry, we characterized the glycophenotype of intestinal epithelia as well as CD4+ and CD8+ T cells isolated both from spleen (systemic level) and colon subepithelial cells/lamina propia (local level). The gene expression profile for five galectins (Gal1, Gal3, Gal4, Gal8, Gal9, all of them highly relevant to the gut immune homeostasis) was analyzed by RT-qPCR. Galectin-1 expression is predominantly local, with the highest levels in lamina propria; in opposition, Galectin-8 showed an increased expression at the epithelial/subepithelial compartment. Aditionally, colonization by commensal bacteria caused a three-fold downregulation of Gal1 expression in epithelial and lamina propria compartments without altering the expression of the other endogenous lectins under study. T cells (CD4+ or CD8+) from untreated mice presented a distinctive glycophenotype when isolated from subepithelia or from lamina propria, indicating that these cell populations could present differential responsiveness to Galectins. Moreover, the presence of commensal bacteria influences CD4+ and CD8+ T cells glycophenotype locally (but not at the systemic level), both when compared to controls and between T cell populations. The results summarized in this work give a new insight into how galectin-glycan interactions in the host could be influenced by commensal microbiota and contribute to intestinal homeostasis.