Intestinal epithelial cells: at the interface of the microbiota and mucosal immunity
The human gastrointestinal tract houses a large number of commensal microbes known as the microbiota. Disruption of microbial diversity has been strongly linked to increased infection susceptibility, indicating that commensal bacteria contribute to prevention of pathogenic infection; however, current studies largely lack investigation into the mechanisms underlying key host-commensal interactions. We have discovered that colonization of mice with a commensal strain of Enterococcus leads to improved intestinal barrier function and decreased infection-induced mortality. We went on to characterize a mechanism by which an enzyme from these bacteria activates intestinal epithelial cells (IECs) to increase barrier defenses in mammalian hosts. Ectopic expression of the enzyme in non-protective and probiotic bacteria was sufficient to enhance intestinal barrier function and confer resistance against S. Typhimurium and Clostridium difficile pathogenesis. These studies demonstrate that specific factors from commensal bacteria can be used to improve host barrier function and limit the pathogenesis of distinct enteric infections. The overall aim of my new research group at the University of Cambridge is to gain mechanistic insights into how IECs can be fine-tuned by specific microbial stimuli to control intrinsic pathogen resistance and modulate local and systemic immune responses.
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