The Staphylococcus superantigen SElX inhibits neutrophil function
New article in PLOS Pathogens reports the first superantigen able to manipulate both innate and adaptive human immune systems
The newest paper from our lab, "The Staphylococcus aureus superantigen SElX is a bifunctional toxin that inhibits neutrophil function", has just been published in PLOS Pathogens. Congratulations to Stephen Tuffs, the first author of the paper!
This is the article 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.
For more information, you can find the article in this link.
Tuffs SW, James DBA, Bestebroer J, Richards AC, Goncheva MI, O’Shea M, et al. (2017) The Staphylococcus aureus superantigen SElX is a bifunctional toxin that inhibits neutrophil function. PLoS Pathog 13(9): e1006461.