The Staphylococcus aureus superantigen SElX is a bifunctional toxin that inhibits neutrophil function.

Autor: Stephen W Tuffs, David B A James, Jovanka Bestebroer, Amy C Richards, Mariya I Goncheva, Marie O'Shea, Bryan A Wee, Keun Seok Seo, Patrick M Schlievert, Andreas Lengeling, Jos A van Strijp, Victor J Torres, J Ross Fitzgerald
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: PLoS Pathogens, Vol 13, Iss 9, p e1006461 (2017)
Druh dokumentu: article
ISSN: 1553-7366
1553-7374
DOI: 10.1371/journal.ppat.1006461
Popis: 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.
Databáze: Directory of Open Access Journals
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