Extracellular Membrane Vesicles from Lactobacilli Dampen IFN-γ Responses in a Monocyte-Dependent Manner

被引:47
作者
Forsberg, Manuel Mata [1 ]
Bjorkander, Sophia [1 ]
Pang, Yanhong [2 ]
Lundqvist, Ludwig [2 ]
Ndi, Mama [3 ]
Ott, Martin [3 ]
Escriba, Irene Buesa [1 ]
Jaeger, Marie-Charlotte [1 ]
Roos, Stefan [2 ]
Sverremark-Ekstrom, Eva [1 ]
机构
[1] Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, Stockholm, Sweden
[2] Swedish Univ Agr Sci, Dept Mol Sci, Uppsala, Sweden
[3] Stockholm Univ, Dept Biochem & Biophys, Stockholm, Sweden
基金
瑞典研究理事会;
关键词
LACTIC-ACID BACTERIA; RHAMNOSUS GG DNA; INTERFERON-GAMMA; INTESTINAL INFLAMMATION; PROBIOTIC BACTERIA; MONONUCLEAR-CELLS; GUT MICROBIOTA; IMMUNE CELLS; METABOLITES; EXPRESSION;
D O I
10.1038/s41598-019-53576-6
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:13
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