title: Staphylococcus aureus-derived factors induce IL-10, IFN-γ and IL-17A-expressing FOXP3+CD161+ T-helper cells in a partly monocyte-dependent manner.
abstract: Staphylococcus aureus (S. aureus) is a human pathogen as well as a frequent colonizer of skin and mucosa. This bacterium potently activates conventional T-cells through superantigens and it is suggested to induce T-cell cytokine-production as well as to promote a regulatory phenotype in T-cells in order to avoid clearance. This study aimed to investigate how S. aureus impacts the production of regulatory and pro-inflammatory cytokines and the expression of CD161 and HELIOS by peripheral CD4(+)FOXP3(+) T-cells. Stimulation of PBMC with S. aureus 161:2-cell free supernatant (CFS) induced expression of IL-10, IFN-γ and IL-17A in FOXP3(+) cells. Further, CD161 and HELIOS separated the FOXP3(+) cells into four distinct populations regarding cytokine-expression. Monocyte-depletion decreased S. aureus 161:2-induced activation of FOXP3(+) cells while pre-stimulation of purified monocytes with S. aureus 161:2-CFS and subsequent co-culture with autologous monocyte-depleted PBMC was sufficient to mediate activation of FOXP3(+) cells. Together, these data show that S. aureus potently induces FOXP3(+) cells and promotes a diverse phenotype with expression of regulatory and pro-inflammatory cytokines connected to increased CD161-expression. This could indicate potent regulation or a contribution of FOXP3(+) cells to inflammation and repression of immune-suppression upon encounter with S. aureus.
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors.forename: Sophia
authors.initials: S
authors.lastname: Björkander
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Hell
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Johansson
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors.forename: Manuel Mata
authors.initials: MM
authors.lastname: Forsberg
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors.forename: Gintare
authors.initials: G
authors.lastname: Lasaviciute
authors.affiliation: Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Roos
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Holmlund
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Sverremark-Ekström
mesh_terms: D018920:Coculture Techniques; D051858:Forkhead Transcription Factors; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000382:microbiology*; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000235:genetics; D013211:Staphylococcus aureus / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C573415:IFNG protein, human; C508609:IL10 protein, human; C508717:IL17A protein, human; D020381:Interleukin-17; C527203:KLRB1 protein, human; D055651:NK Cell Lectin-Like Receptor Subfamily B; D016753:Interleukin-10; D007371:Interferon-gamma