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
A Peptide Antagonist of CD28 Signaling Attenuates Toxic Shock and Necrotizing Soft-Tissue Infection Induced by Streptococcus pyogenes / Ramachandran G; Tulapurkar ME; Harris KM; Arad G; Shirvan A; Shemesh R; Detolla LJ; Benazzi C; Opal SM; Kaempfer R; Cross AS.. - In: THE JOURNAL OF INFECTIOUS DISEASES. - ISSN 0022-1899. - STAMPA. - 207:12(2013), pp. 1869-1877. [10.1093/infdis/jit104]
A Peptide Antagonist of CD28 Signaling Attenuates Toxic Shock and Necrotizing Soft-Tissue Infection Induced by Streptococcus pyogenes
BENAZZI, CINZIA;
2013
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 infectionI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.