Evidence for superantigen involvement in severe group A streptococcal tissue infections

Host-pathogen interactions were studied in tissue biopsy samples from patie nts with severe invasive group A streptococcus (GAS) infections. Skin, subc utaneous tissue, and fascia biopsy samples were divided into clinical grade 1 (no evidence of inflammation [n = 7]) or clinical grade 2 (inflamed tiss ue-erythema and edema including cellulitis, fasciitis, and necrotizing fasc iitis [n = 24]). In situ imaging demonstrated significantly higher bacteria l load in biopsy samples of higher clinical grade (P <.05), and the bacteri al load correlated with the in vivo expression of the superantigen streptoc occal pyrogenic exotoxin F (P<.02). Increased expression of the interleukin -1 cytokines and significantly higher expression of tumor necrosis factor-b eta, interferon-gamma, and the homing receptors CC chemokine receptor 5, CD 44, and cutaneous lymphocyte-associated antigen (P<.002-.05) were observed in biopsy samples of higher clinical grade. Thus, the cytokine profile at t he local site of infection mimics that of a typical superantigen cytokine r esponse. The findings of this study demonstrate a critical role for superan tigens and Th1 cytokines in GAS tissue infections.