Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.
Nat Rev Gastroenterol Hepatol. 2020 May;17(5):263-278. doi: 10.1038/s41575-019-0261-4. Epub 2020 Feb 26.
The human gastrointestinal tract is colonized by trillions of microorganisms that interact with the host to maintain structural and functional homeostasis. Acting as the interface between the site of the highest microbial burden in the human body and the richest immune compartment, a single layer of intestinal epithelial cells specializes in nutrient absorption, stratifies microorganisms to limit colonization of tissues and shapes the responses of the subepithelial immune cells. In this Review, we focus on the expression, regulation and functions of Toll-like receptors (TLRs) in the different intestinal epithelial lineages to analyse how epithelial recognition of bacteria participates in establishing homeostasis in the gut. In particular, we elaborate on the involvement of epithelial TLR signalling in controlling crypt dynamics, enhancing epithelial barrier integrity and promoting immune tolerance towards the gut microbiota. Furthermore, we comment on the regulatory mechanisms that fine-tune TLR-driven immune responses towards pathogens and revisit the role of TLRs in epithelial repair after injury. Finally, we discuss how dysregulation of epithelial TLRs can lead to the generation of dysbiosis, thereby increasing susceptibility to colitis and tumorigenesis.
人类胃肠道定植着数以万亿计的微生物，这些微生物与宿主相互作用，以维持结构和功能的稳态。作为人体中微生物负荷最高部位和免疫组织最丰富部位之间的界面，单层肠道上皮细胞专门负责营养吸收，将微生物分层以限制组织定植，并塑造黏膜下免疫细胞的反应。在这篇综述中，我们重点关注 Toll 样受体 (TLR) 在不同肠道上皮谱系中的表达、调节和功能，以分析上皮细胞对细菌的识别如何参与肠道内的稳态建立。特别地，我们详细阐述了上皮 TLR 信号在控制隐窝动力学、增强上皮屏障完整性以及促进对肠道微生物群的免疫耐受中的作用。此外，我们还评论了精细调节 TLR 驱动的免疫反应以针对病原体的调控机制，并重新审视 TLR 在损伤后上皮修复中的作用。最后，我们讨论了上皮 TLR 的失调如何导致菌群失调的产生，从而增加了结肠炎和肿瘤发生的易感性。
