Immunophysiologie et pathogénèse des interactions hôte-bactérie dans le système entérohépatique.

Chercheurs boursiers - Junior 1 | Concours 2012-2013

Alfredo Menendez

Université de Sherbrooke


Domaine : Maladies infectieuses et immunitaires

The intestines, the liver and the biliary tree form the enterohepatic system. This research is part of a long-term program targeting the understanding of the molecular communication between bacteria, the intestines and the liver, and how this communication impacts the function of the enterohepatic system in health and disease. In this proposal, I will investigate the molecular mechanisms by which biliary function modulates intestinal physiology and immunity, more specifically, the function of intestinal Paneth cells, which are responsible of producing multiple antimicrobial peptides and proteins (AMPP) important to control the growth of the commensal intestinal microbiota and to protect against bacterial infections. I will also conduct research to understand how enterohepatic bacterial infections alter biliary function. I have generated preliminary results suggesting that bile acids control the synthesis of Paneth cells AMPP and that in turn, enterohepatic bacterial infections disrupt biliary function and utilize this as a mechanism of immunopathogenesis. My objectives are: (i) to study the effects of bile acids on Paneth cell antimicrobial function; (ii) to identify the mechanisms of bile acids-mediated regulation of Paneth cell synthesis of AMPP and (iii) to study the molecular mechanisms underlying bacterial-induced alterations of hepatic and enteric biliary functions. I will use an array of advanced molecular and cellular biology techniques and several animal models of bacterial infections, in collaboration with other colleagues with expertise in specific areas relevant for the research.
This research targets important, unexplored areas of intestinal and hepatobiliary physiology and immunology, which are relevant to the understanding and management of enterohepatic diseases. It aims to study the molecular basis of various fundamental hepatobiliary and intestinal functions, and their relationship with bacterial pathogenesis. It should produce original data on the regulation of the intestinal antimicrobial function and the interaction of bacteria with the hepatobiliary system.