Similarities and Differences Between Staphylococcal and Streptococcal Toxic Shock Syndromes in Children: Results From a 30-Case Cohort

Javouhey, Étienne; Bolze, Pierre‐Adrien; Jamen, Claire; Lina, Gérard; Badiou, Cédric; Poyart, Claire; Portefaix, Aurélie; Tristan, Anne; Laurent, François; Bes, Michèle; Vandenesch, François; Gilletand, Yves; Dauwalder, Olivier

doi:10.3389/fped.2018.00360

Cited by 15 publications

(25 citation statements)

References 41 publications

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“…Our results of a Vβ2-specific response to GAS superantigens, as well as TSST-1, is of particular importance considering that skewed Vβ profiles, involving either expansion or depletion of Vβ2-expressing CD3 + cells, have been reported in superantigen-associated toxic shock cases caused by either S. aureus or GAS (7, 8, 41). Taken together, with Vβ2 being the dominant Vβ expressed by human MAIT cells, this provides an explanation to the high frequency of superantigen-triggered cytokine production in MAIT cells compared with the total CD3 + compartment.…”

Section: Discussionmentioning

confidence: 58%

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MAIT Cells Are Major Contributors to the Cytokine Response in Group A Streptococcal Toxic Shock Syndrome

Emgård

Bergsten

McCormick

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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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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Section: Discussionmentioning

confidence: 58%

“…Superantigen involvement in patients with STSS was proposed by studies on peripheral blood demonstrating a skewed Vβ repertoire in T cells during the acute phase (6–8). Only limited data are available on the cytokine responses in patients, but an initial report by Sriskandan et al (9) demonstrated elevated levels of TNFβ (lymphotoxin-α).…”

mentioning

confidence: 99%

MAIT Cells Are Major Contributors to the Cytokine Response in Group A Streptococcal Toxic Shock Syndrome

Emgård

Bergsten

McCormick

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…Considering that neither SEG and SEI nor SSA showed significant differences when human monocytes were treated with them, we could suggest that this first step of infection, which is essential for bacterial dissemination and the subsequent disease prognosis, does not explain the discrepancy of progression to the TSST observed among toxins belonging to different species (66). Nevertheless, it is clear that TSS involves other components of the pathogens which are not evaluated in the present work.…”

Section: Discussionmentioning

confidence: 65%

“…Asterisks represent statistical significance with respect to the untreated cells in each treatment: ****p < 0.0001, ns, non-significant difference. Hashes represent statistical significance with respect to cells treated only with SAgs in each treatment: #### p < 0.0001. staphylococcal and streptococcal TSS differ in their clinical signs, origin of infection, and prognosis (66,78). In order to elucidate if egc SAgs and SSA shared comparable effects on innate immune system cells, we studied both types of toxins.…”

Section: Discussionmentioning

confidence: 99%

egc Superantigens Impair Monocytes/Macrophages Inducing Cell Death and Inefficient Activation

et al. 2020

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Bacterial superantigens (SAgs) are enterotoxins that bind to MHC-II and TCR molecules, activating as much as 20% of the T cell population and promoting a cytokine storm which enhances susceptibility to endotoxic shock, causing immunosuppression, and hindering the immune response against bacterial infection. Since monocytes/macrophages are one of the first cells SAgs find in infected host and considering the effect these cells have on directing the immune response, here, we investigated the effect of four non-classical SAgs of the staphylococcal egc operon, namely, SEG, SEI, SEO, and SEM on monocytic-macrophagic cells, in the absence of T cells. We also analyzed the molecular targets on APCs which could mediate SAg effects. We found that egc SAgs depleted the pool of innate immune effector cells and induced an inefficient activation of monocytic-macrophagic cells, driving the immune response to an impaired proinflammatory profile, which could be mediated directly or indirectly by interactions with MHC class II. In addition, performing surface plasmon resonance assays, we demonstrated that non-classical SAgs bind the gp130 molecule, which is also present in the monocytic cell surface, among other cells.

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“…7 STSS is a complication in 2%-15% of children (vs. 3%-28% in adults) and can carry a CFR of up to 28%. [8][9][10] The principal sites of iGAS infection in children are the skin and the lungs. 2,11,12 Other iGAS clinical syndromes include osteoarthritis and meningitis, which, although rare, are more common in children than in adults.…”

mentioning

confidence: 99%

Clinical Description and Outcomes of Australian Children With Invasive Group A Streptococcal Disease

Thielemans

Oliver

McMinn

et al. 2020

Pediatric Infectious Disease Journal

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Background: Invasive group A streptococcal disease is a severe infection with a high case fatality rate, estimated to cause more than 150,000 deaths per year worldwide. The clinical presentation of this infection is variable, and early diagnosis can be challenging. There are few data on its short-and longer-term outcomes, especially in children. The aim of this study was to assess the clinical presentation, management and short-and longer-term outcomes of invasive group A streptococcal disease in children in Australia. Methods: We undertook a prospective surveillance study of children with laboratory-confirmed invasive group A streptococcus disease admitted to 7 sentinel tertiary and quaternary pediatric hospitals in Australia between July 2016 and June 2018. We collected demographic and clinical data and contacted patients 6 months after discharge to assess longer-term outcomes. Results: We enrolled 181 children, 7 days to 16 years of age. The principal site of invasive infection was blood (126 children, 69.6%), and the most frequent clinical presentation was pneumonia in 46 children (25.4%). Twentysix children developed streptococcal toxic shock syndrome (14.4%), and 74 had severe disease (40.9%), including 71 admitted to the intensive care unit. Five children died (2.8%). At discharge and 6 months, 29.3% and 15.2% of the children had persisting health problems, respectively. Conclusions: Invasive group A streptococcal infection in Australian children is frequently severe and has a high long-term morbidity burden, highlighting the need for strengthened clinical care pathways, epidemiological surveillance and prevention strategies.

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Similarities and Differences Between Staphylococcal and Streptococcal Toxic Shock Syndromes in Children: Results From a 30-Case Cohort

Cited by 15 publications

References 41 publications

MAIT Cells Are Major Contributors to the Cytokine Response in Group A Streptococcal Toxic Shock Syndrome

MAIT Cells Are Major Contributors to the Cytokine Response in Group A Streptococcal Toxic Shock Syndrome

egc Superantigens Impair Monocytes/Macrophages Inducing Cell Death and Inefficient Activation

Clinical Description and Outcomes of Australian Children With Invasive Group A Streptococcal Disease

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