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dc.contributor.authorEmgård, Johanna
dc.contributor.authorBergsten, Helena
dc.contributor.authorMcCormick, John K
dc.contributor.authorBarrantes, Israel
dc.contributor.authorSkrede, Steinar
dc.contributor.authorSandberg, Johan K
dc.contributor.authorNorrby-Teglund, Anna
dc.date.accessioned2019-12-02T15:33:36Z
dc.date.available2019-12-02T15:33:36Z
dc.date.issued2019-11-26
dc.identifier.citationProc Natl Acad Sci U S A. 2019 Nov 26. pii: 1910883116. doi: 10.1073/pnas.1910883116.en_US
dc.identifier.issn1091-6490
dc.identifier.pmid31772015
dc.identifier.doi10.1073/pnas.1910883116
dc.identifier.urihttp://hdl.handle.net/10033/622036
dc.description.abstractStreptococcal toxic shock syndrome (STSS) is a rapidly progressing, life-threatening, systemic reaction to invasive infection caused by group A streptococci (GAS). GAS superantigens are key mediators of STSS through their potent activation of T cells leading to a cytokine storm and consequently vascular leakage, shock, and multiorgan failure. Mucosal-associated invariant T (MAIT) cells recognize MR1-presented antigens derived from microbial riboflavin biosynthesis and mount protective innate-like immune responses against the microbes producing such metabolites. GAS lack de novo riboflavin synthesis, and the role of MAIT cells in STSS has therefore so far been overlooked. Here we have conducted a comprehensive analysis of human MAIT cell responses to GAS, aiming to understand the contribution of MAIT cells to the pathogenesis of STSS. We show that MAIT cells are strongly activated and represent the major T cell source of IFNγ and TNF in the early stages of response to GAS. MAIT cell activation is biphasic with a rapid TCR Vβ2-specific, TNF-dominated response to superantigens and a later IL-12- and IL-18-dependent, IFNγ-dominated response to both bacterial cells and secreted factors. Depletion of MAIT cells from PBMC resulted in decreased total production of IFNγ, IL-1β, IL-2, and TNFβ. Peripheral blood MAIT cells in patients with STSS expressed elevated levels of the activation markers CD69, CD25, CD38, and HLA-DR during the acute compared with the convalescent phase. Our data demonstrate that MAIT cells are major contributors to the early cytokine response to GAS, and are therefore likely to contribute to the pathological cytokine storm underlying STSS.en_US
dc.language.isoenen_US
dc.publisherNational Academy of Sciencesen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectMAIT cellsen_US
dc.subjectStreptococcus pyogenesen_US
dc.subjectcytokineen_US
dc.subjectsuperantigensen_US
dc.titleMAIT Cells Are Major Contributors to the Cytokine Response in Group A Streptococcal Toxic Shock Syndrome.en_US
dc.typeArticleen_US
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalProceedings of the National Academy of Sciences (USA)en_US
refterms.dateFOA2019-12-02T15:33:36Z
dc.source.journaltitleProceedings of the National Academy of Sciences of the United States of America


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