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Cecum gene expression signatures in germ-free WT mice colonized with microbiota from WT or Card9-/- mice and infected with Citrobacter rodentium induced colitis

ABSTRACT: It is crucial to decipher the host-microbiota interactions as they are involved in intestinal homeostasis and diseases. Caspase Recruitment Domain 9 (Card9) is an inflammatory bowel disease (IBD) susceptibility gene coding for an adapter protein for innate immunity toward many microorganisms. Card9-/- mice are more susceptible to colitis induced by Citrobacter rodentium as a result of impaired of the IL-22 pathway. C. rodentium is a natural mouse pathogen widely used to model human infections with Enteropathogenic Escherichia coli and Enterohaemorrhagic E. coli. To explore the role of the gut microbiota in the susceptibility of Card9-/- mice to C. rodentium infection, we colonized WT germ-free (GF) mice with the microbiota of WT (WT-->GF) or Card9-/- (Card9-/- -->GF) mice and challenged them with C. rodentium. Card9-/- -->GF mice were more susceptible than WT-->GF mice to C. rodentium. To examine the mechanisms responsible for this defect, we compared the cecum transcriptomes of WT -->GF and Card9-/- -->GF mice before and during C. rodentium-induced colitis. The number of down-regulated and up-regulated genes on day 12 after C. rodentium infection was lower in Card9-/- -->GF mice than WT-->GF mice. Card9-/- -->GF mice showed a significant down-regulation of gut morphogenesis and wound healing pathways suggesting that recovery is impaired in Card9-/- -->GF mice after C. rodentium infection. Immune response and cell division pathways were up-regulated in WT-->GF mice but not in Card9-/- -->GF confirming the defect of global response to infection when only the Card9-/- microbiota was transferred. The most induced and differentially expressed genes between Card9-/- -->GF and WT-->GF mice on day 4 after C. rodentium infection were Reg3g (encoding REGIIIγ) and Reg3b (encoding REGIIIβ). Overall design: Germ-free (GF) C57BL/6 wild-type (WT) mice were inoculated by oral gavage with fresh stools from conventional WT (WT-->GF) or Card9-/- (Card9-/- -->GF) mice. Three weeks after the colonization, WT-->GF and Card9-/- -->GF mice were infected by oral gavage with 1x10^9 CFU of C. rodentium strain DBS100. 5 mice of each groups (WT-->GF and Card9-/- -->GF) were sacrified before infection. 6 mice of each group were sacrified 4 days after infection, 5 mice of each group were sacrified at day 12 and 3 WT-->GF mice and 5 Card9-/- -->GF mice were sacrified at day 22.

INSTRUMENT(S): Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Probe Name version)


PROVIDER: GSE90577 | GEO | 2017-11-25



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In association with innate and adaptive immunity, the microbiota controls the colonisation resistance against intestinal pathogens. Caspase recruitment domain 9 (CARD9), a key innate immunity gene, is required to shape a normal gut microbiota. Card9-/- mice are more susceptible to the enteric mouse pathogen Citrobacter rodentium that mimics human infections with enteropathogenic and enterohaemorrhagic Escherichia coli. Here, we examined how CARD9 controls C. rodentium infection susceptibility th  ...[more]

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