Intestinal epithelial cell toll-like receptor 5 regulates the intestinal microbiota to prevent low-grade inflammation and metabolic syndrome in mice.
Intestinal epithelial cell toll-like receptor 5 regulates the intestinal microbiota to prevent low-grade inflammation and metabolic syndrome in mice.
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DOI：
10.1053/j.gastro.2014.08.033
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发表时间：
2014-12
期刊：
影响因子：
29.4
通讯作者：
Gewirtz AT
中科院分区：
文献类型：
--
作者：
Chassaing B;Ley RE;Gewirtz AT
与野生型小鼠相比，缺乏识别鞭毛蛋白的受体toll样受体5（TLR 5-null小鼠）的小鼠具有改变的肠道微生物群组成;它们发展为低度炎症，代谢综合征，并且容易患结肠炎。肠上皮细胞（IEC）与树突状细胞（DC）TLR 5在介导这些表型中的相对作用尚不清楚;据报道，肠道微生物群组成的改变反映了畜牧业实践，而不是TLR 5的损失。我们使用允许与作为对照的共同饲养的兄弟姐妹进行比较的育种方案产生了在IEC或DC中具有特异性Tlr 5破坏的小鼠。我们产生了具有侧接Tlr 5的LoxP位点的C57 BL/6小鼠。这些小鼠与表达Cre重组酶的小鼠杂交，Cre重组酶由绒毛蛋白或CD 11 c启动子调节，以产生分别缺乏IEC（TLR 5 ΔIEC）或DC（TLR 5 ΔDC）表达的TLR 5的小鼠。使用Tlr 5 fl/fl同胞作为对照。断奶后，小鼠按性别和基因型或仅按性别圈养（基因型共同圈养）。对小鼠进行了基础表型检查，包括微生物群组成;我们还分析了对致病菌挑战、葡聚糖硫酸钠给药和高脂饮食的反应。与之前TLR 5缺失小鼠的发现相似，在两种饲养条件下，与其同胞对照相比，TLR 5 ΔIEC小鼠具有低度炎症（轻度脾肿大、结肠缩短和脂质运载蛋白-2粪便水平升高）、代谢综合征、无法清除致病菌，并且易于发生结肠炎。TLR 5 ΔIEC小鼠中这种炎症的发展通过给予抗生素消除，并且与微生物群定位以及粪便脂多糖和鞭毛蛋白水平的改变相关。微生物群的组成根据基因型比根据住房更紧密地聚集。从DC的TLR 5的损失并不与炎症相关的表型的发展或微生物群组成的改变相关，但导致鞭毛蛋白诱导的白细胞介素22（IL 22）的产生的完全损失。在小鼠中，鞭毛蛋白激活DC上的TLR 5导致IL 22产生。IEC上TLR 5的表达调节肠道微生物群的组成和定位，预防与肠道炎症相关的疾病。
Mice lacking the receptor toll-like receptor 5 (TLR5-null mice), which recognizes flagellin, have an altered intestinal microbiota composition compared to wild-type mice; they develop low-grade inflammation, metabolic syndrome, and are prone to colitis. The relative roles of intestinal epithelial cell (IEC) vs dendritic cell (DC) TLR5 in mediating these phenotypes is not clear; modification of intestinal microbiota composition has been reported to reflect animal husbandry practices rather than loss of TLR5. We generated mice with specific disruption of Tlr5 in IEC or DC using a breeding scheme that allowed comparison with co-housed siblings, as controls. We generated C57BL/6 mice with LoxP sites flanking Tlr5. These mice were crossed with mice expressing Cre recombinase, regulated by the villin or CD11c promoters, to generate mice that lacked expression of TLR5 by IEC (TLR5ΔIEC) or DC (TLR5ΔDC), respectively. Tlr5fl/fl siblings were used as controls. Upon weaning, mice were housed by sex and genotype or by sex only (genotypes cohoused). Mice were examined for basal phenotypes, including microbiota composition; we also analyzed responses to pathobiont challenge, dextran sodium sulfate administration, and high-fat diets. Similar to previous findings from TLR5-null mice, TLR5ΔIEC mice had low-grade inflammation (mild splenomegaly, shortened colons, and increased fecal levels of lipocalin-2), metabolic syndrome, an inability to clear pathobionts, and were prone to develop colitis compared to their sibling controls, under both housing conditions. Development of this inflammation in the TLR5ΔIEC mice was eliminated by administration of antibiotics, and associated with alterations in localization of microbiota and levels of fecal lipopolysaccharide and flagellin. The composition of the microbiota clustered more closely according to genotype than housing. Loss of TLR5 from DC did not associate with development of inflammation-associated phenotypes or alterations in the composition of the microbiota, but resulted in complete loss of flagellin-induced production of interleukin 22 (IL22). In mice, flagellin activation of TLR5 on DC leads to IL22 production. Expression of TLR5 on IEC regulates the composition and localization of the intestinal microbiota, preventing diseases associated with intestinal inflammation.
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影响因子：
4.8
作者：
Hobert, ME;Sands, KA;Madara, JL
通讯作者：
Madara, JL
DOI：
10.1038/ismej.2012.8
发表时间：
2012-08
期刊：
The ISME journal
影响因子：
--
作者：
通讯作者：
--
硫化氢在炎症病理学中的作用。
影响因子：
3.2
作者：
Bhatia M
通讯作者：
Bhatia M
影响因子：
3.7
作者：
Chassaing B;Srinivasan G;Delgado MA;Young AN;Gewirtz AT;Vijay-Kumar M
通讯作者：
Vijay-Kumar M
DOI：
10.1007/978-1-61779-513-8_13
发表时间：
2012-01-01
期刊：
MUCINS: METHODS AND PROTOCOLS
影响因子：
--
作者：
Johansson, Malin E. V.;Hansson, Gunnar C.
通讯作者：
Hansson, Gunnar C.