title: Evidence for superantigen involvement in severe group a streptococcal tissue infections.
abstract: Host-pathogen interactions were studied in tissue biopsy samples from patients with severe invasive group A streptococcus (GAS) infections. Skin, subcutaneous tissue, and fascia biopsy samples were divided into clinical grade 1 (no evidence of inflammation [n=7]) or clinical grade 2 (inflamed tissue--erythema and edema including cellulitis, fasciitis, and necrotizing fasciitis [n=24]). In situ imaging demonstrated significantly higher bacterial load in biopsy samples of higher clinical grade (P<.05), and the bacterial load correlated with the in vivo expression of the superantigen streptococcal pyrogenic exotoxin F (P<.02). Increased expression of the interleukin-1 cytokines and significantly higher expression of tumor necrosis factor-beta, interferon-gamma, and the homing receptors CC chemokine receptor 5, CD44, and cutaneous lymphocyte-associated antigen (P<.002-.05) were observed in biopsy samples of higher clinical grade. Thus, the cytokine profile at the local site of infection mimics that of a typical superantigen cytokine response. The findings of this study demonstrate a critical role for superantigens and Th1 cytokines in GAS tissue infections.
authors.affiliation: Center for Infectious Medicine, Karolinska Institutet, Department of Medicine, Huddinge University Hospital, SE-141 86 Stockholm, Sweden. Anna.Norrby-Teglund@medhs.ki.se
authors.forename: A
authors.initials: A
authors.lastname: Norrby-Teglund
authors.forename: P
authors.initials: P
authors.lastname: Thulin
authors.forename: B S
authors.initials: BS
authors.lastname: Gan
authors.forename: M
authors.initials: M
authors.lastname: Kotb
authors.forename: A
authors.initials: A
authors.lastname: McGeer
authors.forename: J
authors.initials: J
authors.lastname: Andersson
authors.forename: D E
authors.initials: DE
authors.lastname: Low
mesh_terms: D001426:Bacterial Proteins / Q000032:analysis*; D001706:Biopsy; D002481:Cellulitis / Q000276:immunology* / Q000382:microbiology; D016207:Cytokines / Q000032:analysis; D004890:Erythema / Q000276:immunology* / Q000382:microbiology; D005098:Exotoxins / Q000032:analysis*; D005205:Fascia / Q000276:immunology / Q000382:microbiology; D005208:Fasciitis / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008565:Membrane Proteins; D016201:Receptors, Lymphocyte Homing / Q000032:analysis; D012867:Skin / Q000276:immunology / Q000382:microbiology; D013290:Streptococcal Infections / Q000276:immunology* / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000145:classification / Q000276:immunology*; D018089:Superantigens / Q000032:analysis* / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; D005098:Exotoxins; D008565:Membrane Proteins; D016201:Receptors, Lymphocyte Homing; C117980:SpeA protein, Streptococcus pyogenes; D018089:Superantigens; C027951:erythrogenic toxin