The Staphylococcus aureus superantigen SElX is a bifunctional toxin that inhibits neutrophil function: SElX Inhibits Neutrophil Function

Stephen Tuffs, David James, Jovanka Bestebroer, Amy Richards, Mariya Goncheva, Marie O'Shea, Bryan A. Wee, Keun Seok Seo, Patrick M Schlievert, Andreas Lengeling, Jos A G van Strijp, Victor J Torres, Jonathan Fitzgerald

Research output: Contribution to journalArticlepeer-review

Abstract

Bacterial superantigens (SAgs) cause Vβ-dependent T-cell proliferation leading to immune dysregulation associated with the pathogenesis of life-threatening infections such as toxic shock syndrome, and necrotizing pneumonia. Previously, we demonstrated that staphylococcal enterotoxin-like toxin X (SElX) from Staphylococcus aureus is a classical superantigen that exhibits T-cell activation in a Vβ-specific manner, and contributes to the pathogenesis of necrotizing pneumonia. Here, we discovered that SElX can also bind to neutrophils from human and other mammalian species and disrupt IgG-mediated phagocytosis. Site-directed mutagenesis of the conserved sialic acid-binding motif of SElX abolished neutrophil binding and phagocytic killing, and revealed multiple glycosylated neutrophil receptors for SElX binding. Furthermore, the neutrophil binding-deficient mutant of SElX retained its capacity for T-cell activation demonstrating that SElX exhibits mechanistically independent activities on distinct cell populations associated with acquired and innate immunity, respectively. Finally, we demonstrated that the neutrophil-binding activity rather than superantigenicity is responsible for the SElX-dependent virulence observed in a necrotizing pneumonia rabbit model of infection. Taken together, we report the first example of a SAg, that can manipulate both the innate and adaptive arms of the human immune system during S. aureus pathogenesis.
Original languageEnglish
Article numbere1006461
JournalPLoS Pathogens
Volume13
Issue number9
DOIs
Publication statusPublished - 7 Sept 2017

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