Functional genomic studies of the intestinal response to a foodborne enteropathogen in a humanized gnotobiotic mouse model

Marc Lecuit, Justin L. Sonnenburg, Pascale Cossart, Jeffrey I. Gordon

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

Members of the genus Listeria provide a model for defining host responses to invasive foodborne enteropathogens. Active translocation of Listeria monocytogenes 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 wildtype (WT) or mutant L. monocytogenes strains, or its nonpathogenic noninvasive relative Listeria innocua, or with Bacteroides thetaiotaomicron, a prominent gut symbiont. Mouse Gene-Chips, combined with Ingenuity Pathway software, were used to identify canonical signaling pathways that comprise the response to WT L. monocytogenes versus the other species. Gain- and loss-of-function experiments with L. innocua and L. monocytogenes, respectively, demonstrated that the 773-member transcriptional signature of the response to WT L. monocytogenes is largely conserved in the ΔinlA mutant. Internalin-dependent responses include down-regulation of gene networks involved in various aspects of lipid, amino acid, and energy metabolism and up-regulation of immunoinflammatory responses. The host response is markedly attenuated in a listeriolysin-deficient (Δhly) mutant despite its ability to be translocated to the lamina propria. Together, these studies establish that hly, rather than bacterial invasion of the lamina propria mediated by InlA, is a dominant determinant of the intensity of the host response to L. monocytogenes infection via the oral route.

Original languageEnglish
Pages (from-to)15065-15072
Number of pages8
JournalJournal of Biological Chemistry
Volume282
Issue number20
DOIs
StatePublished - May 18 2007

Fingerprint

Dive into the research topics of 'Functional genomic studies of the intestinal response to a foodborne enteropathogen in a humanized gnotobiotic mouse model'. Together they form a unique fingerprint.

Cite this