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Probiotic Lactobacilli Modulate Staphylococcus aureus-Induced Activation of Conventional and Unconventional T cells and NK Cells
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
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Number of Authors: 8
2016 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 7, 273Article in journal (Refereed) Published
Abstract [en]

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), gamma delta 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-gamma 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.

Place, publisher, year, edition, pages
2016. Vol. 7, 273
Keyword [en]
cell-free supernatant, immune modulation, lactobacilli, NK cells, probiotic, T cells, Staphylococcus aureus, superantigens
National Category
Biological Sciences Immunology in the medical area
URN: urn:nbn:se:su:diva-132953DOI: 10.3389/fimmu.2016.00273ISI: 000379401800001PubMedID: 27462316OAI: diva2:956464
Available from: 2016-08-30 Created: 2016-08-26 Last updated: 2016-09-28
In thesis
1. Infant gut microbiota, immune responses and allergic disease during childhood
Open this publication in new window or tab >>Infant gut microbiota, immune responses and allergic disease during childhood
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The early-life microbiota is important for postnatal immune maturation and implied in immune mediated diseases. The aim of this work was to study specific species of bacteria in the gut microbiota and relate them to immune function and allergic disease during childhood.

In paper I we investigated gut bacteria in feces from infants included in a prospective allergy cohort. We found that children with non-allergic parents were more likely to be colonized with a group of lactobacilli. Further, lactobacilli colonization was more prevalent in children remaining non-allergic, regardless of allergic heredity. In paper II we related the infant gut bacteria to immune function at two years of age. Infant Staphylococcus (S.) aureus colonization associated with increased immune responsiveness, whereas co-colonization with S. aureus and lactobacilli associated with reduced responses. In paper III we investigated T regulatory (Treg) cell phenotype and cytokine production during childhood, and related S. aureus and lactobacilli colonization to Treg phenotype at the age of two. The Treg population matured with age, regarding phenotype and cytokine production. Furthermore, infant S. aureus colonization associated with Treg phenotype at the age of two. In paper IV we investigated the in vitro peripheral blood mononuclear cells responses to soluble factors produced by lactobacilli and S. aureus. Both T- and natural killer cells responded with cytokine production, degranulation and proliferation after S. aureus and simultaneous culture with lactobacilli could dampen the S. aureus-induced responses.

Taken together this thesis shows that the gut microbiota is altered in children who develop allergies, and that early life bacteria associate with immune function. Our in vitro findings support that lactobacilli modulate immune maturation and responses, and that early lactobacilli-colonization may be important for a properly regulated maturation of the immune system.

Place, publisher, year, edition, pages
Stockholm: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 2014. 82 p.
National Category
Research subject
urn:nbn:se:su:diva-108425 (URN)978-91-7649-036-5 (ISBN)
Public defence
2014-11-28, De Geersalen, Geovetenskapens hus, Svante Arrhenius väg 14, 10:00 (English)

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 4: Manuscript.

Available from: 2014-11-06 Created: 2014-10-23 Last updated: 2016-09-27Bibliographically approved
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Johansson, Maria A.Björkander, SophiaMata Forsberg, ManuelQazi, Khaleda RahmanEberl, Matthias
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