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.
journal_name
PLoS Pathogjournal_title
PLoS pathogensauthors
Tuffs SW,James DBA,Bestebroer J,Richards AC,Goncheva MI,O'Shea M,Wee BA,Seo KS,Schlievert PM,Lengeling A,van Strijp JA,Torres VJ,Fitzgerald JRdoi
10.1371/journal.ppat.1006461subject
Has Abstractpub_date
2017-09-07 00:00:00pages
e1006461issue
9eissn
1553-7366issn
1553-7374pii
PPATHOGENS-D-17-00747journal_volume
13pub_type
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