Double-Stranded RNA Derived from Lactic Acid Bacteria Augments Th1 Immunity via Interferon-β from Human Dendritic Cells.

Double-Stranded RNA Derived from Lactic Acid Bacteria Augments Th1 Immunity via Interferon-β from Human Dendritic Cells.
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源自乳酸细菌的双链RNA通过人树突状细胞增强了Th1免疫力。

DOI:
10.3389/fimmu.2018.00027
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发表时间:
2018
影响因子:
7.3
通讯作者:
Tsuji NM
Tsuji NM
中科院分区:
医学2区
文献类型:
--
作者:
Kawashima T;Ikari N;Watanabe Y;Kubota Y;Yoshio S;Kanto T;Motohashi S;Shimojo N;Tsuji NM

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乳酸菌(LAB)是小肠中的主要寄生菌之一,并且已知有助于维持保护性免疫和免疫稳态。然而,目前还没有证据表明LAB对人体免疫细胞的益生菌作用涉及细胞机制。在这里,我们证明了LAB双链RNA(dsRNA)触发人树突状细胞(DC)产生干扰素-β(IFN-β),这激活了产生IFN-γ的T细胞。响应于LAB的来自人DC的白细胞介素-12(IL-12)分泌通过细菌dsRNA的消耗而消除,并且通过中和IFN-β而减弱,表明LAB dsRNA主要激活IFN-β/IL-12途径。此外,LAB诱导DC分泌IL-12被内体酸化的抑制所消除,证实了LAB的内体消化的关键作用。在人幼稚CD 4 + T细胞和BDCA 1 + DC的共培养中,用含有dsRNA的LAB刺激的DC诱导产生IFN-γ的T细胞。这些结果表明,由LAB激活的人DC增强Th 1免疫,这取决于响应细菌dsRNA的IFN-β分泌。
Lactic acid bacteria (LAB) are one of the major commensal species in the small intestine and known for contributing to maintenance of protective immunity and immune homeostasis. However, currently there has been no evidence regarding the cellular mechanisms involved in the probiotic effects of LAB on human immune cells. Here, we demonstrated that LAB double-stranded RNA (dsRNA) triggered interferon-β (IFN-β) production by human dendritic cells (DCs), which activated IFN-γ-producing T cells. Interleukin-12 (IL-12) secretion from human DCs in response to LAB was abrogated by depletion of bacterial dsRNA, and was attenuated by neutralizing IFN-β, indicating LAB dsRNA primarily activated the IFN-β/IL-12 pathway. Moreover, the induction of IL-12 secretion from DCs by LAB was abolished by the inhibition of endosomal acidification, confirming the critical role of the endosomal digestion of LAB. In a coculture of human naïve CD4+ T cells and BDCA1+ DCs, DCs stimulated with LAB containing dsRNA induced IFN-γ-producing T cells. These results indicate that human DCs activated by LAB enhance Th1 immunity depending on IFN-β secretion in response to bacterial dsRNA.
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