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

• Published in: Scientific reports 2019-11, Vol.9 (1), p.17109-17109, Article 17109
• Main Authors: Mata Forsberg, Manuel, Björkander, Sophia, Pang, Yanhong, Lundqvist, Ludwig, Ndi, Mama, Ott, Martin, Escribá, Irene Buesa, Jaeger, Marie-Charlotte, Roos, Stefan, Sverremark-Ekström, Eva
• Format: Article
• Language: English
• Subjects: 13; 13/1; 13/21; 13/31; 631/250/127; 631/326/41; 82/16; 82/79; Adolescent; Adult; Aged; Cell activation; Cytokines; Cytokines - metabolism; Extracellular vesicles; Extracellular Vesicles - drug effects; Extracellular Vesicles - immunology; Extracellular Vesicles - metabolism; Female; Healthy Volunteers; Humanities and Social Sciences; Humans; Immunologi inom det medicinska området; Immunology in the medical area; Inflammation; Interferon-gamma - pharmacology; Interleukin 1; Interleukin 1 receptor antagonist; Interleukin-17 - metabolism; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Lactobacillus; Lactobacillus - physiology; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Male; Membrane vesicles; Middle Aged; Monocytes; Monocytes - drug effects; Monocytes - immunology; Monocytes - metabolism; multidisciplinary; Peripheral blood mononuclear cells; Proteome - analysis; Science; Science (multidisciplinary); T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Young Adult; γ-Interferon
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-53576-6

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-γ 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-γ dampening activity. Indeed, addition of recombinant IL-1ra to stimulated PBMC resulted in reduced IFN-γ 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.