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Lactobacilli are probiotic commensal bacteria and potent modulators of immunity. When present in the gut or supplemented as probiotics, they beneficially modulate  ex vivo  immune responsiveness. Further, factors derived from several lactobacilli strains act immune regulatory  in vitro . In contrast,  Staphylococcus aureus  ( S. aureus ) is known to induce excessive T cell activation. In this study, we aimed to investigate  S. aureus -induced activation of human mucosal-associated invariant T cells (MAIT cells), γδ T cells, NK cells, as well as of conventional CD4 +  and CD8 +  T cells  in vitro . Further, we investigated if lactobacilli-derived factors could modulate their activation. PBMC were cultured with  S. aureus  161:2 cell-free supernatants (CFS), staphylococcal enterotoxin A or CD3/CD28-beads alone, or in combination with  Lactobacillus rhamnosus  GG-CFS or  Lactobacillus reuteri  DSM 17938-CFS and activation of T and NK cells was evaluated.  S. aureus -CFS induced IFN-γ and CD107a expression as well as proliferation. Costimulation with lactobacilli-CFS dampened lymphocyte-activation in all cell types analyzed. Preincubation with lactobacilli-CFS was enough to reduce subsequent activation, and the absence of APC or APC-derived IL-10 did not prevent lactobacilli-mediated dampening. Finally, lactate selectively dampened activation of unconventional T cells and NK cells. In summary, we show that molecules present in the lactobacilli-CFS are able to directly dampen  in vitro  activation of conventional and unconventional T cells and of NK cells. This study provides novel insights on the immune-modulatory nature of probiotic lactobacilli and suggests a role for lactobacilli in the modulation of induced T and NK cell activation.

Probiotic Lactobacilli Modulate Staphylococcus aureus-Induced Activation of Conventional and Unconventional T cells and NK Cells