ArticleProceedings of the National Academy of Sciences of the United States of America2019
MAIT Cells Are Major Contributors to the Cytokine Response in Group A Streptococcal Toxic Shock Syndrome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 61 citations in OpenAlex.
- Type 2 diabetes mellitus wake-up call: fatal streptococcal toxic shock syndrome triggered by the M1(UK) Streptococcus pyogenes - a case report with genomic insights.BMC infectious diseases · 2026Article
- Group A Streptococcal Virulence Factors and Vaccine Development-An Update.Microorganisms · 2026Review
- Gastrointestinal MAIT cells in chronic HIV-1 infection.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- The "Cairo Accord"- towards the eradication of RHD: revisited (2026).Frontiers in cardiovascular medicine · 2026Review
- NKG2A-mediated immune modulation of natural killer cells by Staphylococcus aureus.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Immune profiling in subclinical secondary dengue-infected cases reveals adaptive immune signatures correlated to protection from severe dengue.Cell host & microbe · 2025Article
- Hantaan virus infection induces human mucosal-associated invariant T cell pyroptosis through IRE1α pathway.Communications biology · 2025Article
- Proinflammatory synergy between protease and superantigen streptococcal pyogenic exotoxins.Infection and immunity · 2025Article
- Human MAIT cell response profiles biased toward IL-17 or IL-10 are distinct effector states directed by the cytokine milieu.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Global spread of Streptococcus pyogenes A genomics-supported narrative review.FEMS microbiology reviews · 2025Review
- Distinct MAIT cell phenotypes associated with sepsis clinical outcome in emergency department patients.Clinical & translational immunology · 2025Article
- A mini review of the pathogenesis of acute rheumatic fever and rheumatic heart disease.Frontiers in cellular and infection microbiology · 2025Review
- The Emerging Roles and Therapeutic Potential of Unconventional T Cells in Sepsis.Journal of inflammation research · 2025Review
- The intricate pathogenicity of Group AVirulence · 2024Review
- Novel insights into the immune response to bacterial T cell superantigens.Nature reviews. Immunology · 2024Review
- Reduced interleukin-18 secretion by human monocytic cells in response to infections with hyper-virulent Streptococcus pyogenes.Journal of biomedical science · 2024Article
- MAIT cells in bacterial infectious diseases: heroes, villains, or both?Clinical and experimental immunology · 2023Review
- Natural Killer T Cell Diversity and Immunotherapy.Cancers · 2023Review
- The nuclear cytokine IL-37a controls lethal cytokine storms primarily via IL-1R8-independent transcriptional upregulation of PPARγ.Cellular & molecular immunology · 2023Article
- HLA-II-Dependent Neuroimmune Changes in Group A Streptococcal Necrotizing Fasciitis.Pathogens (Basel, Switzerland) · 2023Article
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Authors and funding
7 authors at 4 institutions in 4 countries.
Funding
Abstract
Streptococcal 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.
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