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J Infect Dis. 2013 Jun 15;207(12):1869-77. doi: 10.1093/infdis/jit104. Epub 2013 Mar 14.

A peptide antagonist of CD28 signaling attenuates toxic shock and necrotizing soft-tissue infection induced by Streptococcus pyogenes.

Author information

  • 1Center for Vaccine Development, University of Maryland Medical School, Baltimore, Baltimore, MD 21201, USA.

Abstract

Staphylococcus aureus and group A Streptococcus pyogenes (GAS) express superantigen (SAg) exotoxin proteins capable of inducing lethal shock. To induce toxicity, SAgs must bind not only to the major histocompatibility complex II molecule of antigen-presenting cells and the variable β chain of the T-cell receptor but also to the dimer interface of the T-cell costimulatory receptor CD28. Here, we show that the CD28-mimetic peptide AB103 (originally designated "p2TA") protects mice from lethal challenge with streptococcal exotoxin A, as well as from lethal GAS bacterial infection in a murine model of necrotizing soft-tissue infection. Administration of a single dose of AB103 increased survival when given up to 5 hours after infection, reduced inflammatory cytokine expression and bacterial burden at the site of infection, and improved muscle inflammation in a dose-dependent manner, without compromising cellular and humoral immunity. Thus, AB103 merits further investigation as a potential therapeutic in SAg-mediated necrotizing soft-tissue infection.

KEYWORDS:

CD28; group A S. pyogenes; necrotizing soft tissue infection; peptide antagonist; superantigen

PMID:
23493729
PMCID:
PMC3654752
DOI:
10.1093/infdis/jit104
[PubMed - indexed for MEDLINE]
Free PMC Article
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