Projects per year
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.
|Publication status||Published - 7 Sep 2017|
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- 2 Finished
ISP 3 2017/22 Improving Animal Health and Welfare
1/04/17 → 31/03/22
Innate immunity and endemic diseases in livestock species
Collie, D., Beard, P., Bishop, S., Bronsvoort, M., Burt, D., Fitzgerald, R., Freeman, T., Gally, D., Gill, A., Glass, E., Hocking, P., Hope, J., Hume, D., Kaiser, P., Mabbott, N., McLachlan, G., Morrison, L., Stevens, J., Stevens, M. & Watson, M.
1/04/12 → 31/03/17
- Royal (Dick) School of Veterinary Studies - Personal Chair of Molecular Bacteriology
Person: Academic: Research Active