Epithelial crosstalk at the microbiota-mucosal interface
Epithelial crosstalk at the microbiota-mucosal interface
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DOI：
10.1073/pnas.1000092107
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发表时间：
2011-03-15
影响因子：
11.1
通讯作者：
van Baarlen, Peter
中科院分区：
文献类型：
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作者：
Wells, Jerry M.;Rossi, Oriana;van Baarlen, Peter
本文概述了肠上皮细胞（IEC）如何识别细菌以及它们如何维持宿主-细菌共生。肠上皮的内分泌、杯状细胞和肠上皮细胞表达一系列模式识别受体（PRR）以感知微生物的存在。最具特征的是Toll样受体（TLR）和核苷酸寡聚化结构域样受体（NLR），它们在病原体识别和诱导先天效应物和炎症中起关键作用。PRR信号的几种适应性变化已经在肠道中进化，以避免对驻留微生物群的不受控制和潜在破坏性的炎症反应。IEC中的PRR信号传导用于维持上皮的屏障功能，包括分泌型伊加（sIgA）的产生。此外，IEC在设定粘膜的免疫抑制张力以抑制对无害的管腔抗原的过度反应中发挥重要作用。这包括通过上皮分泌的细胞因子调节树突状细胞（DC）、巨噬细胞和淋巴细胞功能。这些免疫机制在很大程度上依赖于微生物的IEC识别，并且与敲除小鼠中的几项研究一致，这些研究表明上皮中的TLR信号传导在维持体内平衡方面具有深刻的有益作用。
This article provides an overview of how intestinal epithelial cells (IEC) recognize commensals and how they maintain host-bacterial symbiosis. Endocrine, goblet cells, and enterocytes of the intestinal epithelium express a range of pattern recognition receptors (PRR) to sense the presence of microbes. The best characterized are the Toll-like receptors (TLR) and nucleotide oligomerization domain-like receptors (NLR), which play a key role in pathogen recognition and the induction of innate effectors and inflammation. Several adaptations of PRR signaling have evolved in the gut to avoid uncontrolled and potentially destructive inflammatory responses toward the resident microbiota. PRR signaling in IEC serve to maintain the barrier functions of the epithelium, including the production of secretory IgA (sIgA). Additionally, IECs play a cardinal role in setting the immunosuppressive tone of the mucosa to inhibit overreaction against innocuous luminal antigens. This includes regulation of dendritic cells (DC), macrophage and lymphocyte functions by epithelial secreted cytokines. These immune mechanisms depend heavily on IEC recognition of microbes and are consistent with several studies in knockout mice that demonstrate TLR signaling in the epithelium has a profoundly beneficial role in maintaining homeostasis.