Citrobacter Infection and Wnt Signaling

Gut flora generally contributes to a healthy environment, but both commensal and pathogenic bacteria that influence the innate and adaptive immune responses can cause acute and/or chronic mucosal inflammation. Citrobacter rodentium is a member of the family of enteropathogens that provide an excellent in vivo model to investigate host-pathogen interactions in real time. It is the etiologic agent of transmissible murine colonic hyperplasia, and inflammation following C. rodentium infection is dependent upon the genetic background. Ongoing and completed studies in this model have established that Wnt/beta-catenin, Notch, and phosphatidylinositol 3-kinase pathways regulate colonic crypt hyperplasia, whereas epithelial-stromal cross talk, mediated by MEK/ERK/nuclear factor.B signaling, regulates inflammation and/or colitis in susceptible strains. The C. rodentium-induced hyperplastic state also increases the susceptibility to either mutagenic insult or in mice heterozygous for the Apc gene. The ability to modulate the host response to C. rodentium infection therefore provides an opportunity to delineate the mechanisms that determine mucosal hyperplasia, intestinal inflammation, and/or neoplasia as disease outcomes.