#SeminarIRSJD · Vesícules extracel·lulars de la microbiota intestinal com a moduladors de la homeòstasi intestinal i salut humana
- Dra. Laura Baldomà, jefa del grupo Microbiota intestinal · IRSJD
Seminario exclusivo para personal de la institución. Si deseas obtener el enlace de conexión contacta con frecerca.comunicacio(ELIMINAR)@sjd.es
Resumen
The intestine is crucial in controlling human health. Intestinal epithelial and immune cells are constantly exposed to millions of microbes that deeply impact on intestinal barrier and immune function. This microbial community, referred as the gut microbiota, is an important partner that performs essential functions for the host. The mucus layer that covers the epithelium prevents luminal bacteria from accessing cells of the intestinal mucosa. Therefore, microbiota-host communication mainly depends on secreted factors. Growing body of evidence indicates that extracellular membrane vesicles (MVs) mediate microbiota functions by delivering into host cells effector molecules that modulate signalling pathways. Our group aims at studying the molecular mechanisms used by microbiota MVs to modulate host immune and defence responses, using as a model Escherichia coli. We have shown that MVs from gut resident E. coli strains are internalized by epithelial cells through clathrin-mediated endocytosis and regulate basal inflammation through activation of the NOD1-signalling pathway. Microbiota MVs reinforce the epithelial barrier and reduce gut permeability by modulating tight junction proteins at the transcriptional and post-translational levels. We have also shown that MVs are a mechanism used by the gut microbiota to steadily prime the innate immune system, activating dendritic cells (DCs) in a strain-specific manner. Differential regulation of microRNAs in DCs accounts for the specific effects. MVs from the probiotic EcN prime DCs to drive strong Th1 responses that are crucial to fight against pathogens, whereas MVs from harmless commensals orchestrate Treg responses that are critical for immune tolerance in the intestine. At present we are focused on exploring new activities of microbiota MVs that could envisage their potential application to human health, particularly in the prevention/treatment of enteric virus infections, inflammatory bowel disease or cancer.