Research and Development Division, Kikkoman Corporation, Chiba, Japan.
Biomedical Research Institute, National Institute for Advanced Industrial Science and Technology (AIST), Tsukuba, Japan.
Front Immunol. 2018 Jan 23;9:27. doi: 10.3389/fimmu.2018.00027. eCollection 2018.
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.
乳酸菌（LAB）是小肠中主要的共生物种之一，其作用是维持保护性免疫和免疫稳态。然而，目前尚无关于 LAB 对人类免疫细胞的益生菌作用的细胞机制的证据。在这里，我们证明 LAB 的双链 RNA（dsRNA）触发了人类树突状细胞（DC）产生干扰素-β（IFN-β），从而激活了产生 IFN-γ 的 T 细胞。通过耗尽细菌 dsRNA 或中和 IFN-β，可阻断 LAB 诱导的人 DC 中白细胞介素-12（IL-12）的分泌，表明 LAB dsRNA 主要激活了 IFN-β/IL-12 途径。此外，通过抑制内体酸化，可消除 LAB 对 DC 中 IL-12 分泌的诱导，证实了 LAB 内体消化的关键作用。在人幼稚 CD4 T 细胞和 BDCA1 DC 的共培养物中，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，LAB 激活的人 DC 通过响应细菌 dsRNA 分泌 IFN-β来增强 Th1 免疫。
