Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
PLoS One. 2012;7(4):e35918. doi: 10.1371/journal.pone.0035918. Epub 2012 Apr 24.
Toll-like receptor (TLR) 5 has been shown to maintain intestinal homeostasis and regulate host defense against enterobacterial infection. However, how TLR5 expression is regulated and its function in the intestine have not been fully elucidated. Here we demonstrate that mucosal dendritic cells (DCs), but not splenic DCs, express high levels of TLR5 protein. Alternatively spliced Tlr5 transcripts were identified but it did not explain the selective expression of TLR5 on mucosal DCs. Treatment with various bacterial ligands downregulated BMDC TLR5 expression, while retinoic acid and host stromal cell-derived signals promoted TLR5 expression in a TGF-β-independent mechanism. Signaling through TLR5 restrained regulatory T (Treg) cell generation, and accordingly, TLR5(-/-) mice displayed increased frequencies of Foxp3(+) Treg cells in the intestinal lamina propria. Our data indicate that bacterial and host factors differentially regulate DC TLR5 expression. TLR5 signaling regulates immune responses towards the microbiota via modulation of the Treg/effector T cell balance.
Toll 样受体（TLR）5 被证明可以维持肠道内稳态，并调节宿主对肠杆菌感染的防御。然而，TLR5 的表达如何受到调节及其在肠道中的功能尚未完全阐明。在这里，我们证明黏膜树突状细胞（DCs）而非脾 DCs 表达高水平的 TLR5 蛋白。鉴定了选择性剪接的 Tlr5 转录本，但这并不能解释 TLR5 在黏膜 DCs 上的选择性表达。用各种细菌配体处理可下调 BMDC TLR5 的表达，而维甲酸和宿主基质细胞衍生的信号通过 TGF-β 非依赖性机制促进 TLR5 的表达。TLR5 信号转导通过调节调节性 T（Treg）细胞的生成来限制效应 T 细胞的生成，因此，TLR5(-/-) 小鼠在肠道固有层中显示出更高频率的 Foxp3(+) Treg 细胞。我们的数据表明，细菌和宿主因素差异调节 DC TLR5 的表达。TLR5 信号通过调节 Treg/效应 T 细胞平衡来调节对微生物群的免疫反应。
