Research suggests novel mechanism of superantigen-induced pathology

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Researchers have described a novel mechanism of superantigen-induced pathology, identifying a subpopulation of T cells as the key source of pro-inflammatory cytokines after exposure to superantigens.

Superantigens are bacterial exotoxins, namely secreted by Staphylococcus aureus and Streptococcus pyogenes, which target T cells, triggering a ‘cytokine storm’. This aggressive immune response can have severe consequences often observed in toxic shock syndrome. The mechanisms behind this response are poorly understood, with identification of key modulators an area of research priority.

This study, published recently in PLOS Biology, identified mucosa-associated invariant T (MAIT) cells as a powerful producer of cytokines after superantigen exposure. The researchers used primary human cells and mouse models to study the hyperresonse of MAIT cells to these bacterial toxins, demonstrating that exposure triggered robust activation of MAIT cells and production of inflammatory mediators.

In addition, the team discovered that such an intense response of MAIT cells rapidly resulted in their exhaustion, interfering with their ability to act in antimicrobial host defense. This immunosuppressive state, or anergic phenotype, could lead to increased susceptibility to secondary, opportunistic infections.

Senior author Mansour Haeryfar (Western University, Ontario, Canada) explained: “In this context, MAIT cells are actually disease-causing as opposed to protective. We have shown that MAIT cells are the most powerful source of an inflammatory mediator called interferon-γ, thus likely contributing to morbidity associated with toxic shock syndrome and similar superantigen-mediated illnesses.”

This research is the first to report this novel mechanism of superantigen-induced immunopathology and immunosuppression, identifying MAIT cells as a key mediator. The team suggest that targeting these cells may also present a therapeutic target for mediating superantigen pathology.

Haeryfar concluded: “Based on our findings, we propose that timely and efficient therapies that target MAIT cells will likely benefit the patients by preventing uncontrolled inflammation and also by relieving immunosuppression.”

Sources: Shaler CR, Choi J, Rudak PT et al. MAIT cells launch a rapid, robust and distinct hyperinflammatory response to bacterial superantigens and quickly acquire an anergic phenotype that impedes their cognate antimicrobial function: Defining a novel mechanism of superantigen-induced immunopathology and immunosuppression. PLOS Biol. doi:10.1371/journal.pbio.2001930 (Epub) (2017); www.eurekalert.org/pub_releases/2017-06/p-bst061317.php

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