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GABA potentiate the immunoregulatory effects of Lactobacillus brevis BGZLS10-17 via ATG5-dependent autophagy in vitro

  • 2020-01-28
  • Scientific Reports 10(1)
    • S. S. Bajić
    • Jelena Đokić
    • M. Dinić
    • S. Tomić
    • N. Popović
    • Emilija Brdarić
    • N. Golić
    • M. Tolinački

Abstract

The characterization of mechanisms involved in the positive effects of probiotic bacteria in various pathophysiological conditions is a prerogative for their safe and efficient application in biomedicine. We have investigated the immunological effects of live bacteria-free supernatant collected from GABA-producing Lactobacillus brevis BGZLS10-17 on Concanavalin A-stimulated mesenteric lymph node cells (MLNC), an in vitro model of activated immune cells. We have shown that GABA containing and GABA-free supernatant of Lactobacillus brevis BGZLS10-17 have strong immunoregulatory effects on MLNC. Further, GABA produced by this strain exhibit additional inhibitory effects on proliferation, IFN-γ and IL-17 production by MLNC, and the expression of MHCII and CD80 on antigen presenting cells. At the other hand, GABA-containing supernatants displayed the strongest stimulatory effects on the expression of immunoregulatory molecules, such as Foxp3+, IL-10, TGF-β, CTLA4 and SIRP-α. By looking for the mechanisms of actions, we found that supernatants produced by BGZLS10-17 induce autophagy in different MLNC, such as CD4+ and CD8+ T lymphocytes, NK and NKT cells, as well as antigen presenting cells. Further, we showed that the stimulation of Foxp3+, IL-10 and TGF-β expression by BGZLS10-17 produced GABA is completely mediated by the induction of ATG5 dependent autophagy, and that other molecules in the supernatants display GABA-, ATG5-, Foxp3+-, IL-10- and TGF-β- independent, immunoregulatory effects.

Research Insights

SupplementHealth OutcomeEffect TypeEffect Size
Lactobacillus brevis MAK11L82BEnhanced AutophagyBeneficial
Moderate
Lactobacillus brevis MAK11L82BEnhanced Immunoregulatory FunctionBeneficial
Large
Lactobacillus brevis MAK11L82BEnhanced Immunoregulatory Molecule ActivityBeneficial
Moderate
Lactobacillus brevis MAK11L82BReduced Immune Cell ProliferationBeneficial
Large

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