Extracellular Membrane Vesicles from Lactobacilli Dampen IFN-γ Responses in a Monocyte-Dependent Manner
Extracellular Membrane Vesicles from Lactobacilli Dampen IFN-γ Responses in a Monocyte-Dependent Manner
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DOI：
10.1038/s41598-019-53576-6
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发表时间：
2019-11-19
影响因子：
4.6
通讯作者：
Sverremark-Ekstrom, Eva
中科院分区：
文献类型：
--
作者：
Forsberg, Manuel Mata;Bjorkander, Sophia;Sverremark-Ekstrom, Eva
来源于乳酸杆菌的分泌因子能够抑制促炎细胞因子反应。尽管如此，这些成分的性质和潜在的机制仍然难以捉摸。在这里，我们的目的是确定的成分和机制参与乳杆菌介导的免疫细胞活化的调节。在培养鼠李糖乳杆菌GG和罗伊氏乳杆菌DSM 17938的无细胞上清液（CFS）存在下刺激PBMC，然后评估细胞因子的反应。我们发现乳酸菌- cfs通过可溶性因子以单核细胞依赖的方式有效地抑制T细胞和NK细胞诱导的ifn - γ和IL-17A反应。蛋白质组学阵列分析强调乳酸菌诱导的IL-1受体拮抗剂（ra）是ifn - γ抑制活性的潜在候选物质。事实上，将重组IL-1ra添加到受刺激的PBMC中导致ifn - γ的产生减少。对乳酸菌- cfs的进一步表征表明，存在与乳酸菌- cfs相似的免疫调节活性的胞外膜囊泡。总之，我们已经表明，乳酸菌产生细胞外的mv，它能够以单核细胞依赖的方式抑制促炎细胞因子反应。
Secreted factors derived from Lactobacillus are able to dampen pro-inflammatory cytokine responses. Still, the nature of these components and the underlying mechanisms remain elusive. Here, we aimed to identify the components and the mechanism involved in the Lactobacillus-mediated modulation of immune cell activation. PBMC were stimulated in the presence of the cell free supernatants (CFS) of cultured Lactobacillus rhamnosus GG and Lactobacillus reuteri DSM 17938, followed by evaluation of cytokine responses. We show that lactobacilli-CFS effectively dampen induced IFN-gamma and IL-17A responses from T- and NK cells in a monocyte dependent manner by a soluble factor. A proteomic array analysis highlighted Lactobacillus-induced IL-1 receptor antagonist (ra) as a potential candidate responsible for the IFN-gamma dampening activity. Indeed, addition of recombinant IL-1ra to stimulated PBMC resulted in reduced IFN-gamma production. Further characterization of the lactobacilli-CFS revealed the presence of extracellular membrane vesicles with a similar immune regulatory activity to that observed with the lactobacilli-CFS. In conclusion, we have shown that lactobacilli produce extracellular MVs, which are able to dampen pro-inflammatory cytokine responses in a monocyte-dependent manner.