Functional Genomic Studies of the Intestinal Response to a Foodborne Enteropathogen in a Humanized Gnotobiotic

Members of the genus Listeria provide a model for defining host responses to invasive foodborne enteropathogens. Active translocation of Listeriamonocytogenes across the gut epithelial barrier is mediated by interaction of bacterial internalin (InlA) and its species-specific host receptor, E-cadherin, whereas translocation across Peyer’s patches through M-cells is InlA-independent. To define microbial determinants and molecular correlates of the host response to translocation via these two routes, we colonized germ-free transgenic mice expressing the human enterocyte-associated E-cadherin receptor with wild-type (WT) or mutant L. monocytogenes strains, or its nonpatho-genic noninvasive relative Listeria innocua, or with Bacteroides thetaiotaomicron, a prominent gut symbiont. Mouse Gene-Chips, combinedwith Ingenuity Pathway software, were used to identify canonical signaling pathways that comprise th