AUTHOR=Johansson Maria A. , Björkander Sophia , Mata Forsberg Manuel , Qazi Khaleda Rahman , Salvany Celades Maria , Bittmann Julia , Eberl Matthias , Sverremark-Ekström Eva 

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

JOURNAL=Frontiers in Immunology

VOLUME=7

YEAR=2016

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2016.00273

DOI=10.3389/fimmu.2016.00273

ISSN=1664-3224

ABSTRACT=<p>Lactobacilli are probiotic commensal bacteria and potent modulators of immunity. When present in the gut or supplemented as probiotics, they beneficially modulate <italic>ex vivo</italic> immune responsiveness. Further, factors derived from several lactobacilli strains act immune regulatory <italic>in vitro</italic>. In contrast, <italic>Staphylococcus aureus</italic> (<italic>S. aureus</italic>) is known to induce excessive T cell activation. In this study, we aimed to investigate <italic>S. aureus</italic>-induced activation of human mucosal-associated invariant T cells (MAIT cells), γδ T cells, NK cells, as well as of conventional CD4<sup>+</sup> and CD8<sup>+</sup> T cells <italic>in vitro</italic>. Further, we investigated if lactobacilli-derived factors could modulate their activation. PBMC were cultured with <italic>S. aureus</italic> 161:2 cell-free supernatants (CFS), staphylococcal enterotoxin A or CD3/CD28-beads alone, or in combination with <italic>Lactobacillus rhamnosus</italic> GG-CFS or <italic>Lactobacillus reuteri</italic> DSM 17938-CFS and activation of T and NK cells was evaluated. <italic>S. aureus</italic>-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 <italic>in vitro</italic> 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.</p>