Staphylococcal enterotoxin B in vivo modulates both gamma interferon receptor expression and ligand-induced activation of signal transducer and activator of transcription 1 in T cells

摘要: Superantigens (SAgs) are highly immunostimulatory exotoxins produced by several microorganisms, mainly the gram-positive bacteria Staphylococcus aureus and Streptococcus pyogenes (34, 43). The pathophysiology associated with SAgs is linked to their ability bypass conventional antigen peptide presentation binding major histocompatibility complex class II molecules on antigen-presenting cells without being internally processed then interacting particular external Vβ domains in T-cell receptors of reactive T lymphocytes, thus stimulating proliferation regard for specificity these (25, 32). massive activation induced triggers systemic release proinflammatory cytokines, which has been development toxic shock syndrome. Common syndrome symptoms fever, rash, hypotension, multiple organ system dysfunction, can eventually lead death (4, 34). Administration SAg staphylococcal enterotoxin B (SEB) BALB/c mice a useful model studying some vivo effects superantigens. While excessive gamma interferon (IFN-γ) SEB life-threatening inflammation (17) prevention protective humoral response (5), following inhibition IFN-γ production (15, 39) might favor bacterial dissemination susceptibility reinfections. We therefore believe that study physiological consequences modulation will be rewarding unraveling aspects SAg-induced lethality immunosuppression. An accurate regulation from host required orchestration effective Th1 macrophage-rich inflammatory reactions against microbial infections (8). natural killer (NK) interacts specific cell surface receptor (IFN-γR) expressed all nucleated at modest levels IFN-γR heterodimeric composed two subunits, namely, α chain, exhibits high-affinity ligand properties, β chain (accessory factor), primarily signaling Binding activates through JAK/STAT pathway, leads STAT1α phosphorylation, dimerization, translocation nucleus, where it binds site (GAS) elements promoters IFN-γ-inducible genes modulates transcription inhibited other such as interleukin-6 (IL-6) or IL-10, STAT3-mediated (11, 12). IL-6 IL-10 have found able inhibit differentiation terminate responses (12, 44). even further promote function regulatory (Treg) suppress induce tolerance 37, 39). The hyperresponse immunosuppression follows upon exposure studied extensively. However, studies focused cellular level cytokine secretion but not intracellular response. To gain better understanding mechanism condition immune responsiveness state host, we examined its SEB. Here show mouse acquisition lethal rechallenge correlates clonal expansion phase production. In contrast, IFN-γ/STAT1 STAT3 selectively down-regulated splenic 72 h after first Differential STAT1/STAT3 pathways may involved survival suppressor phenotype stimulation superantigen.