Sorbonne University - Université Pierre et Marie Curie (UPMC), Paris, France.
Avenir Team Gut Microbiota and Immunity, Equipe de Recherche Labélisée (ERL) 1157, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France.
Gut. 2018 Oct;67(10):1836-1844. doi: 10.1136/gutjnl-2017-314195. Epub 2017 Aug 8.
In association with innate and adaptive immunity, the microbiota controls the colonisation resistance against intestinal pathogens. Caspase recruitment domain 9 (), a key innate immunity gene, is required to shape a normal gut microbiota. mice are more susceptible to the enteric mouse pathogen that mimics human infections with enteropathogenic and enterohaemorrhagic . Here, we examined how controls infection susceptibility through microbiota-dependent and microbiota-independent mechanisms.
infection was assessed in conventional and germ-free (GF) wild-type (WT) and mice. To explore the impact of microbiota in infection susceptibility, GF WT mice were colonised with WT (WT→GF) or ( →GF) microbiota before 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.
controls pathogen virulence in a microbiota-independent manner by supporting a specific humoral response. Higher susceptibility to -induced colitis was observed in →GF mice. The microbiota of mice failed to outcompete the monosaccharide-consuming , worsening the infection severity. A polysaccharide-enriched diet counteracted the ecological advantage of and the defective pathogen-specific antibody response in mice.
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.
与先天免疫和适应性免疫相关，微生物群控制着对肠道病原体的定植抵抗。半胱氨酸天冬氨酸蛋白酶募集域 9 ()，一种关键的先天免疫基因，是塑造正常肠道微生物群所必需的。 小鼠更容易感染类似于人类感染肠致病性和肠出血性 的肠道病原体 。在这里，我们研究了 通过依赖于微生物群和不依赖于微生物群的机制来控制感染易感性的方式。
在常规和无菌 (GF) 野生型 (WT) 和 小鼠中评估了 感染。为了探索微生物群在感染易感性中的影响，在 感染前用 WT (WT→GF) 或 ( →GF) 微生物群定植 GF WT 小鼠。通过 16S rDNA 基因测序确定微生物群组成。通过组织学评分和脂联素水平确定炎症严重程度。通过定量 PCR 分析评估微生物群-宿主免疫系统相互作用。
以不依赖于微生物群的方式独立控制病原体毒力，支持特定的体液反应。在 →GF 小鼠中观察到对 -诱导的结肠炎的易感性增加。 小鼠的微生物群未能与消耗单糖的 竞争，从而使感染加重。富含多糖的饮食可以抵消 的生态优势和 小鼠中缺陷的病原体特异性抗体反应。
CARD9 通过控制依赖于微生物群和不依赖于微生物群的病原体毒力来调节对肠道感染的易感性。肠道病原体的遗传易感性可以通过恢复体液免疫和竞争微生物群的饮食干预来克服。
