Commensal DNA limits regulatory T cell conversion and is a natural adjuvant of intestinal immune responses.
Commensal DNA limits regulatory T cell conversion and is a natural adjuvant of intestinal immune responses.
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DOI：
10.1016/j.immuni.2008.08.009
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发表时间：
2008-10-17
期刊：
影响因子：
32.4
通讯作者：
Belkaid, Yasmine
中科院分区：
文献类型：
--
作者：
Hall, Jason A.;Bouladoux, Nicolas;Sun, Cheng Ming;Wohlfert, Elizabeth A.;Blank, Rebecca B.;Zhu, Qing;Grigg, Michael E.;Berzofsky, Jay A.;Belkaid, Yasmine
肠道与共生微生物区系密切接触。然而，共生体如何与细胞沟通以确保免疫动态平衡仍不清楚。在这项研究中，我们发现肠道菌群DNA(GfDNA)通过Toll样受体9参与在肠道内稳态中发挥重要作用。TLR9基因缺陷小鼠的肠道效应部位T细胞(Treg)频率增加，构成IL-17和干扰素-γ的效应T细胞(T细胞)减少。作为补充，gfDNA限制的固有层树突状细胞在体外诱导Treg转化。此外，TLR9−/−小鼠的Treg/Tef不平衡导致对口腔感染和口服疫苗的免疫反应受损，但通过中和Treg可以恢复这种免疫反应。在接受抗生素治疗的小鼠中，受损的肠道免疫反应被重现，并在用gfDNA重建后是可逆的。综上所述，这些数据表明gfDNA是一种通过调节Treg/TJeff平衡来启动肠道反应的天然佐剂。
The intestinal tract is in intimate contact with the commensal microflora. Nevertheless, how commensals communicate with cells to ensure immune homeostasis is still unclear. In this study, we found that gut flora DNA (gfDNA) plays a major role in intestinal homeostasis through toll like receptor 9 engagement. TLR9 deficient mice displayed increased frequencies of CD4+Foxp3+ regulatory T cells (Treg) within intestinal effector sites, and reduced constitutive IL-17 and IFN-γ producing effector T cells (Teff). Complementing this, gfDNA limited lamina propria dendritic cells induced Treg conversion in vitro. Further, Treg/Teff disequilibrium in TLR9−/− mice led to impaired immune responses to oral infection and to oral vaccination, which were rescued through neutralization of Treg. Impaired intestinal immune responses were recapitulated in mice treated with antibiotics and were reversible following reconstitution with gfDNA. Together these data point to gfDNA as a natural adjuvant for priming intestinal responses via modulation of Treg/Teff equilibrium.
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影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
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DOI：
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