Toxic shock syndrome with a cytokine storm caused by Staphylococcus simulans: a case report

Abstract Background Exotoxins secreted from Staphylococcus aureus or Streptococcus pyogenes act as superantigens that induce systemic release of inflammatory cytokines and are a common cause of toxic shock syndrome (TSS). However, little is known about TSS caused by coagulase-negative staphylococci (CoNS) and the underlying mechanisms. Here, we present a rare case of TSS caused by Staphylococcus simulans (S. simulans). Case presentation We report the case of a 75-year-old woman who developed pneumococcal pneumonia and bacteremia from S. simulans following an influenza infection. The patient met the clinical criteria for probable TSS, and her symptoms included fever of 39.5 °C, diffuse macular erythroderma, conjunctival congestion, vomiting, diarrhea, liver dysfunction, and disorientation. Therefore, the following treatment was initiated for bacterial pneumonia complicating influenza A with suspected TSS: meropenem (1 g every 8 h), vancomycin (1 g every 12 h), and clindamycin (600 mg every 8 h). Blood cultures taken on the day after admission were positive for CoNS, whereas sputum and pharyngeal cultures grew Streptococcus pneumoniae (Geckler group 4) and methicillin-sensitive S. aureus, respectively. However, exotoxins thought to cause TSS, such as TSS toxin-1 and various enterotoxins, were not detected. The patient’s therapy was switched to cefazolin (2 g every 8 h) and clindamycin (600 mg every 8 h) for 14 days based on microbiologic test results. She developed desquamation of the fingers on hospital day 8 and was diagnosed with TSS. Conventional exotoxins, such as TSST-1, and S. aureus enterotoxins were not detected in culture samples. The serum levels of inflammatory cytokines, such as neopterin and IL-6, were high. CD8+ T cells were activated in peripheral blood. Vβ2+ population activation, which is characteristic for TSST-1, was not observed in the Vβ usage of CD8+ T cells in T cell receptor Vβ repertoire distribution analysis. Conclusions We present a case of S. simulans-induced TSS. Taken together, we speculate that no specific exotoxins are involved in the induction of TSS in this patient. A likely mechanism is uncontrolled cytokine release (i.e., cytokine storm) induced by non-specific immune reactions against CoNS proliferation.

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OVX836 Heptameric Nucleoprotein Vaccine Generates Lung Tissue-Resident Memory CD8+ T-Cells for Cross-Protection Against Influenza

Frontiers in Immunology ◽

10.3389/fimmu.2021.678483 ◽

2021 ◽

Vol 12 ◽

Author(s):

Judith Del Campo ◽

Julien Bouley ◽

Marion Chevandier ◽

Carine Rousset ◽

Marjorie Haller ◽

...

Keyword(s):

T Cells ◽

Recombinant Protein ◽

Dna Sequence ◽

Cd8 T Cells ◽

Influenza A ◽

Influenza Infection ◽

Influenza Viruses ◽

Protein Vaccine ◽

Memory Cd8 T Cells

Tissue-resident memory (TRM) CD8+ T-cells play a crucial role in the protection against influenza infection but remain difficult to elicit using recombinant protein vaccines. OVX836 is a recombinant protein vaccine, obtained by the fusion of the DNA sequence of the influenza A nucleoprotein (NP) to the DNA sequence of the OVX313 heptamerization domain. We previously demonstrated that OVX836 provides broad-spectrum protection against influenza viruses. Here, we show that OVX836 intramuscular (IM) immunization induces higher numbers of NP-specific IFNγ-producing CD8+ T-cells in the lung, compared to mutant NP (NPm) and wild-type NP (NPwt), which form monomeric and trimeric structures, respectively. OVX836 induces cytotoxic CD8+ T-cells and high frequencies of lung TRM CD8+ T-cells, while inducing solid protection against lethal influenza virus challenges for at least 90 days. Adoptive transfer experiments demonstrated that protection against diverse influenza subtypes is mediated by NP-specific CD8+ T-cells isolated from the lung and spleen following OVX836 vaccination. OVX836 induces a high number of NP-specific lung CD8+ TRM-cells for long-term protection against influenza viruses.

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Staphylococcal Toxic Shock Syndrome Complicating Influenza A Infection in a Young Child

ISRN Pulmonology ◽

10.5402/2011/645718 ◽

2011 ◽

Vol 2011 ◽

pp. 1-3 ◽

Cited By ~ 4

Author(s):

Timothy R. Peters ◽

Dudley E. Hammon ◽

Rima J. Jarrah ◽

Elizabeth L. Palavecino ◽

Elizabeth S. Blakeney ◽

...

Keyword(s):

Toxic Shock Syndrome ◽

Influenza A ◽

Bacterial Culture ◽

Rare Complication ◽

Influenza Infection ◽

Tracheal Aspirate ◽

Upper Respiratory Tract ◽

Toxic Shock ◽

Upper Respiratory ◽

Staphylococcal Toxic Shock Syndrome

Toxic shock syndrome (TSS) is a potentially lethal but rare complication of influenza infection. We report a case of TSS and influenza A infection in a 5-year-old boy without respiratory symptoms, in whom tracheal aspirate bacterial culture grew a toxin-producing strain of Staphylococcus aureus. Bacterial culture of the upper respiratory tract should be considered in patients with influenza-associated toxic shock syndrome.

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Topical exposure to triclosan inhibits Th1 immune responses and reduces T cells responding to influenza infection in mice

PLoS ONE ◽

10.1371/journal.pone.0244436 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0244436

Author(s):

Hillary L. Shane ◽

Sreekumar Othumpangat ◽

Nikki B. Marshall ◽

Francoise Blachere ◽

Ewa Lukomska ◽

...

Keyword(s):

T Cells ◽

Immune Responses ◽

Cd8 T Cells ◽

Healthcare Workers ◽

Influenza A ◽

Influenza Infection ◽

Statistical Significance ◽

Lethal Dose ◽

Respiratory Pathogens ◽

Increased Risk

Healthcare workers concurrently may be at a higher risk of developing respiratory infections and allergic disease, such as asthma, than the general public. Increased incidence of allergic diseases is thought to be caused, in part, due to occupational exposure to chemicals that induce or augment Th2 immune responses. However, whether exposure to these chemical antimicrobials can influence immune responses to respiratory pathogens is unknown. Here, we use a BALB/c murine model to test if the Th2-promoting antimicrobial chemical triclosan influences immune responses to influenza A virus. Mice were dermally exposed to 2% triclosan for 7 days prior to infection with a sub-lethal dose of mouse adapted PR8 A(H1N1) virus (50 pfu); triclosan exposure continued until 10 days post infection (dpi). Infected mice exposed to triclosan did not show an increase in morbidity or mortality, and viral titers were unchanged. Assessment of T cell responses at 10 dpi showed a decrease in the number of total and activated (CD44hi) CD4+ and CD8+ T cells at the site of infection (BAL and lung) in triclosan exposed mice compared to controls. Influenza-specific CD4+ and CD8+ T cells were assessed using MHCI and MHCII tetramers, with reduced populations, although not reaching statistical significance at these sites following triclosan exposure. Reductions in the Th1 transcription factor T-bet were seen in both activated and tetramer+ CD4+ and CD8+ T cells in the lungs of triclosan exposed infected mice, indicating reduced Th1 polarization and providing a potential mechanism for numerical reduction in T cells. Overall, these results indicate that the immune environment induced by triclosan exposure has the potential to influence the developing immune response to a respiratory viral infection and may have implications for healthcare workers who may be at an increased risk for developing infectious diseases.

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Induction of selective anergy by toxic shock syndrome toxin‐1 in CD8 + T cells

Immunology ◽

10.1046/j.1365-2567.1997.00344.x ◽

1997 ◽

Vol 92 (2) ◽

pp. 188-193

Author(s):

Y.‐X. ZHAO† ◽

R. HOLMDAHL ◽

A. TARKOWSKI

Keyword(s):

T Cells ◽

Cd8 T Cells ◽

Toxic Shock Syndrome ◽

Toxic Shock ◽

Toxic Shock Syndrome Toxin

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Superantigenic TCR Vbeta 21.3 signature in Multisystem Inflammatory Syndrome in Children

10.1101/2021.02.11.21251166 ◽

2021 ◽

Author(s):

Marion Moreews ◽

Kenz Le Gouge ◽

Alicia Bellomo ◽

Christophe Malcus ◽

Rémi Pescarmona ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

T Cell ◽

Kawasaki Disease ◽

T Cell Activation ◽

Toxic Shock Syndrome ◽

Healthy Children ◽

Toxic Shock ◽

Hla Dr ◽

Inflammatory Syndrome

AbstractObjectivesMultiple Inflammatory Syndrome in Children (MIS-C) is the most severe pediatric form of COVID-19 and occurs in previously healthy children. MIS-C combines features of Kawasaki disease and Toxic Shock Syndrome (TSS).MethodsChildren with suspected MIS-C were included within the first week of diagnosis and a large scale immunoassay was performed to determein the immunologic signature of these patients.ResultsWe characterized the immunological profile of 27 MIS-C cases in comparison with 4 KD and 4 TSS cases. Similarly to TSS, an increase of serum inflammatory cytokines (IL-6, TNF-a, CD25s) was observed in MIS-C contrasting with low expression of HLA-DR monocytes, a feature often associated with immune paralysis. Expansions of T cells expressing the Vβ21.3 T cell receptor β chain variable region were detected in both CD4 and CD8 subsets in almost 50% of patients and Vβ21.3-positive T cells expressed high level of HLA-DR highlighting their specific activation. TCR sequencing uncovered the polyclonal nature of the Vβ 21.3+ population. SARS-CoV2 antigene-specific production of interferon gamma in T cells was not increased in MIS-C T cells compared to COVID-19 patients suggesting the antigen-specific immune response in MIS-C patients is not pivotal to the manifestation.ConclusionsOur findings argue in favor of a strong activation of the immune system related to a superantigenic immune response in MIS-C with a specific polyclonal Vβ21.3 T cell expansion.Key messagesWhat is already known about this subject ?MIS-C occurs 3-5 weeks after acute SARS-CoV2 infection and overlap features of Toxic Shock syndrome and Kawasaki disease.MIS-C appears different in term of cytokine and autoantibodies generation from KD with subtle signs of T cells activationWhat does this study add?This study demonstrates that Vβ21.3+ CD4 and CD8 T cells are highly increased in about 50% of MIS-C and distinctive of the Vβ2+ expansion observed in toxic shock syndrome in This reflects a specific T cell activation and cytokine release syndrome similar to toxic shock syndromeHow mich this impact on clinical practice or future developments?Vβ21.3+ signature can be available on a short term basis by flowcytometry and represents a signature of the MIS-C.As for TSS, immunomodulating therapies may revert the superantigenic activation and resolve this life threatening pediatric condition.

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Mucosal CD8+ T cell responses induced by an MCMV based vaccine vector confer protection against influenza challenge

10.1101/494864 ◽

2018 ◽

Author(s):

Xiaoyan Zheng ◽

Jennifer Dora Oduro ◽

Julia Désirée Boehme ◽

Lisa Borkner ◽

Thomas Ebensen ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Cd8 T Cells ◽

Cell Response ◽

Influenza A ◽

Clinical Medicine ◽

Cd8 T Cell ◽

T Cell Response ◽

Vaccine Vector ◽

Protective Capacity

Cytomegalovirus (CMV) is a ubiquitous β-herpesvirus that establishes life-long latent infection in a high percentage of the population worldwide. CMV induces the strongest and most durable CD8+ T cell response known in human clinical medicine. Due to its unique properties, the virus represents a promising candidate vaccine vector for the induction of persistent cellular immunity. To take advantage of this, we constructed a recombinant murine CMV (MCMV) expressing an MHC-I restricted epitope from influenza A virus (IAV) H1N1 within the immediate early 2 (ie2) gene. Only mice that were immunized intranasally (i.n.) were capable of controlling IAV infection, despite the greater potency of the intraperitoneally (i.p.) vaccination in inducing a systemic IAV-specific CD8+ T cell response. The protective capacity of the i.n. immunization was associated with its ability to induce IAV-specific tissue-resident memory CD8+ T (CD8TRM) cells in the lungs. Our data demonstrate that the protective effect exerted by the i.n. immunization was critically mediated by antigen-specific CD8+ T cells. CD8TRM cells promoted the induction of IFNγ and chemokines that facilitate the recruitment of antigen-specific CD8+ T cells to the lungs. Overall, our results showed that locally applied MCMV vectors could induce mucosal immunity at sites of entry, providing superior immune protection against respiratory infections.

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Interleukin-10 (IL-10) Produced by Mutant Toxic Shock Syndrome Toxin 1 Vaccine-Induced Memory T Cells Downregulates IL-17 Production and Abrogates the Protective Effect against Staphylococcus aureus Infection

Infection and Immunity ◽

10.1128/iai.00494-19 ◽

2019 ◽

Vol 87 (10) ◽

Author(s):

Kouji Narita ◽

Dong-Liang Hu ◽

Krisana Asano ◽

Akio Nakane

Keyword(s):

Staphylococcus Aureus ◽

T Cells ◽

Infectious Diseases ◽

Protective Effect ◽

Toxic Shock Syndrome ◽

Long Term Memory ◽

Toxic Shock ◽

Content Type ◽

Memory Phase ◽

Toxic Shock Syndrome Toxin

ABSTRACT Development of long-term memory is crucial for vaccine-induced adaptive immunity against infectious diseases such as Staphylococcus aureus infection. Toxic shock syndrome toxin 1 (TSST-1), one of the superantigens produced by S. aureus, is a possible vaccine candidate against infectious diseases caused by this pathogen. We previously reported that vaccination with less toxic mutant TSST-1 (mTSST-1) induced T helper 17 (Th17) cells and elicited interleukin-17A (IL-17A)-mediated protection against S. aureus infection 1 week after vaccination. In the present study, we investigated the host immune response induced by mTSST-1 vaccination in the memory phase, 12 weeks after the final vaccination. The protective effect and IL-17A production after vaccination with mTSST-1 were eliminated because of IL-10 production. In the presence of IL-10-neutralizing monoclonal antibody (mAb), IL-17A production was restored in culture supernatants of CD4+ T cells and macrophages sorted from the spleens of vaccinated mice. Vaccinated mice treated with anti-IL-10 mAb were protected against systemic S. aureus infection in the memory phase. From these results, it was suggested that IL-10 produced in the memory phase suppresses the IL-17A-dependent vaccine effect through downregulation of IL-17A production.

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