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| Status |
Public on Nov 25, 2017 |
| Title |
Cecum gene expression signatures in germ-free WT mice colonized with microbiota from WT or Card9-/- mice and infected with Citrobacter rodentium induced colitis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
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).
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| 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.
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| Contributor(s) |
Lamas B, Pham H, Sokol H |
| Citation(s) |
28790160 |
| Submission date |
Nov 28, 2016 |
| Last update date |
Feb 26, 2018 |
| Contact name |
Bruno LAMAS |
| E-mail(s) |
lamasbruno@hotmail.fr
|
| Organization name |
Unité INSERM 1157/UMR 7203
|
| Department |
CHU St Antoine
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| Lab |
Avenir Team Gut Microbiota and Immunity
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| Street address |
27 rue Chaligny
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| City |
Paris |
| ZIP/Postal code |
75012 |
| Country |
France |
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| Platforms (1) |
| GPL10787 |
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Probe Name version) |
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| Samples (40)
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| Relations |
| BioProject |
PRJNA355113 |
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