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Updated: Feb 25, 2026
Quantitative Polymerase Chain Reaction-based Analyses of Murine Intestinal Microbiota After Oral Antibiotic Treatment
Published on: November 17, 2018
Card9 mediates susceptibility to intestinal pathogens through microbiota modulation and control of bacterial
Bruno Lamas1,2,3,4,5, Marie-Laure Michel5, Nadine Waldschmitt6,7
1Sorbonne University - Université Pierre et Marie Curie (UPMC), Paris, France.
Insights
Caspase recruitment domain 9 (CARD9) influences gut microbiota and immunity, impacting susceptibility to Citrobacter rodentium infection. Diet can overcome genetic susceptibility by restoring immunity and microbiota.
Area of Science:
- Immunology
- Microbiology
- Genetics
Background:
- The gut microbiota plays a crucial role in host defense against intestinal pathogens.
- Caspase recruitment domain 9 (CARD9) is a key innate immunity gene essential for maintaining a healthy gut microbiota.
- Mice lacking CARD9 (Card9-/-) exhibit increased susceptibility to Citrobacter rodentium, a pathogen that models human E. coli infections.
Purpose of the Study:
- To investigate the mechanisms by which CARD9 influences susceptibility to Citrobacter rodentium infection.
- To differentiate between microbiota-dependent and microbiota-independent roles of CARD9 in controlling infection.
Main Methods:
- Citrobacter rodentium infection was studied in conventional and germ-free wild-type and Card9-/- mice.
- Germ-free mice were colonized with either wild-type or Card9-/- microbiota to assess microbiota-driven susceptibility.
- Microbiota composition, inflammation severity, and host-microbiota immune interactions were analyzed.
Main Results:
- CARD9 independently controls pathogen virulence by supporting humoral immune responses.
- Mice colonized with Card9-/- microbiota (Card9→GF) showed increased susceptibility to C. rodentium infection.
- The microbiota from Card9-/- mice was less effective at competing with C. rodentium, exacerbating infection.
- A polysaccharide-rich diet mitigated C. rodentium's advantage and improved the antibody response in Card9-/- mice.
Conclusions:
- CARD9 modulates intestinal infection susceptibility through both microbiota-dependent and independent pathways.
- Dietary interventions can overcome genetic susceptibility by restoring humoral immunity and competitive microbiota.
Objective:
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 through microbiota-dependent and microbiota-independent mechanisms.
Design:
C. rodentium infection was assessed in conventional and germ-free (GF) wild-type (WT) and Card9-/- mice. To explore the impact of Card9-/-microbiota in infection susceptibility, GF WT mice were colonised with WT (WT→GF) or Card9-/- (Card9 →GF) microbiota before C. rodentium infection. Microbiota composition was determined by 16S rDNA gene sequencing. Inflammation severity was determined by histology score and lipocalin level. Microbiota-host immune system interactions were assessed by quantitative PCR analysis.
Results:
CARD9 controls pathogen virulence in a microbiota-independent manner by supporting a specific humoral response. Higher susceptibility to C. rodentium-induced colitis was observed in Card9 →GF mice. The microbiota of Card9-/- mice failed to outcompete the monosaccharide-consuming C. rodentium, worsening the infection severity. A polysaccharide-enriched diet counteracted the ecological advantage of C. rodentium and the defective pathogen-specific antibody response in Card9-/- mice.
Conclusions:
CARD9 modulates the susceptibility to intestinal infection by controlling the pathogen virulence in a microbiota-dependent and microbiota-independent manner. Genetic susceptibility to intestinal pathogens can be overridden by diet intervention that restores humoural immunity and a competing microbiota.
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