Innate Recognition of the Microbiota by TLR1 Promotes Epithelial Homeostasis and Prevents Chronic Inflammation.
Innate Recognition of the Microbiota by TLR1 Promotes Epithelial Homeostasis and Prevents Chronic Inflammation.
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DOI：
10.4049/jimmunol.1701216
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发表时间：
2018-07-01
期刊：
影响因子：
--
通讯作者：
DePaolo RW
中科院分区：
文献类型：
--
作者：
Kamdar K;Johnson AMF;Chac D;Myers K;Kulur V;Truevillian K;DePaolo RW
肠上皮和微生物群之间存在串扰，其功能是维持严格调节的微环境并防止慢性炎症。这种通讯部分是通过宿主编码的先天受体（如Toll样受体）识别细菌蛋白介导的。然而，研究Toll样受体信号传导对结肠稳态的作用的研究给出了可变和相互矛盾的结果。尽管其在小肠肠道感染期间介导免疫的关键作用，但TLR 1介导的微生物源性配体的识别及其对结肠稳态的影响尚未得到充分研究。在这里，我们证明了上皮细胞对微生物组的TLR 1识别缺陷会导致分泌细胞室内的隐窝稳态破坏，包括粘液层缺陷，结肠中的异位潘氏细胞以及隐窝底部快速分裂细胞数量的增加。由于上皮屏障受到干扰，我们发现粘膜相关和易位的肠道细菌增加，慢性低度炎症的特征是谱系阴性Sca 1 + Thy 1hi先天淋巴样细胞增加，这些细胞在结肠损伤和修复模型中加剧炎症并恶化结果。我们的研究结果表明，Toll样受体-1对微生物群的感知可能提供调节结肠上皮的关键信号，从而通过防止细菌附着于粘膜和暴露于潜在的免疫系统来限制炎症。
There is crosstalk between the intestinal epithelium and the microbiota that functions to maintain a tightly regulated microenvironment and prevent chronic inflammation. This communication is partly mediated through the recognition of bacterial proteins by host encoded innate receptors, such as Toll-like Receptors. However, studies examining the role of Toll-like Receptor signaling on colonic homeostasis have given variable and conflicting results. Despite its critical role in mediating immunity during enteric infection of the small intestine, TLR1-mediated recognition of microbiota-derived ligands and their influence on colonic homeostasis has not been well studied. Here, we demonstrate that defective TLR1 recognition of the microbiome by epithelial cells results in disruption of crypt homeostasis specifically within the secretory cell compartment, including a defect in the mucus layer, ectopic Paneth cells in the colon and an increase in the number of rapidly dividing cells at the base of the crypt. As a consequence of the perturbed epithelial barrier, we found an increase in mucosal-associated and translocated commensal bacteria and chronic low-grade inflammation characterized by an increase in lineage-negative, Sca1+Thy1hi innate lymphoid-like cells that exacerbate inflammation and worsen outcomes in a model of colonic injury and repair. Our findings demonstrate that sensing of the microbiota by Toll-like Receptor-1 may provide key signals that regulate the colonic epithelium thereby limiting inflammation through the prevention of bacterial attachment to the mucosa and exposure to the underlying immune system.
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影响因子：
4.6
作者：
Andreu, P;Colnot, S;Romagnolo, B
通讯作者：
Romagnolo, B
影响因子：
32.4
作者：
Guo, Xiaohuan;Qiu, Ju;Tu, Tony;Yang, Xuanming;Deng, Liufu;Anders, Robert A.;Zhou, Liang;Fu, Yang-Xin
通讯作者：
Fu, Yang-Xin
DOI：
10.1038/nri.2016.88
发表时间：
2016-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Johansson ME;Hansson GC
通讯作者：
Hansson GC
影响因子：
5.5
作者：
Farhat, Katja;Riekenberg, Sabine;Ulmer, Artur J.
通讯作者：
Ulmer, Artur J.
影响因子：
30.5
作者：
Bernink, Jochem H.;Peters, Charlotte P.;Spits, Hergen
通讯作者：
Spits, Hergen