Invariant Natural Killer T Cells Are Pathogenic In The Hla-Dr4-Transgenic Humanized Mouse Model Of Toxic Shock Syndrome And Can Be Targeted To Reduce Morbidity
JOURNAL OF INFECTIOUS DISEASES(2017)
Abstract
During toxic shock syndrome (TSS), bacterial superantigens trigger a polyclonal T -cell response leading to a potentially catastrophic "cytokine storm". Whether innate-like invariant natural killer T (iNKT) cells, with remarkable immunomodulatory properties, participate in TSS is unclear. Using genetic and cell depletion approaches, we generated iNKT cell-deficient, superantigen-sensitive HLA-DR4-transgenic (DR4tg) mice, which were compared with their iNKT-sufficient counterparts for responsiveness to staphylococcal enterotoxin B (SEB). Both approaches indicate that iNKT cells are pathogenic in TSS. Importantly, treating DR4tg mice with a T(H)2-polarizing glycolipid agonist of iNKT cells reduced SEB-inflicted morbidity/mortality. Therefore, iNKT cells may constitute an attractive therapeutic target in superantigen-mediated illnesses.
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Key words
Invariant natural killer T cells, Staphylococcus aureus, superantigen, staphylococcal enterotoxin B, toxic shock syndrome, inflammation, cytokines
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