title: PI3K/Akt/mTOR, a pathway less recognized for staphylococcal superantigen-induced toxicity.
abstract: Immunostimulating staphylococcal enterotoxin B (SEB) and related superantigenic toxins cause diseases in humans and laboratory animals by activating cells of the immune system. These toxins bind directly to the major histocompatibility complex (MHC) class II molecules on antigen-presenting cells and specific V&#946; regions of T-cell receptors (TCR), resulting in hyperactivation of both T lymphocytes and monocytes/macrophages. Activated host cells produce excessive amounts of proinflammatory cytokines and chemokines, especially tumor necrosis factor &#945;, interleukin 1 (IL-1), IL-2, interferon &#947; (IFN&#947;), and macrophage chemoattractant protein 1 causing clinical symptoms of fever, hypotension, and shock. The well-explored signal transduction pathways for SEB-induced toxicity downstream from TCR/MHC ligation and interaction of cell surface co-stimulatory molecules include the mitogen-activated protein kinase cascades and cytokine receptor signaling, culminating in NF&#954;B activation. Independently, IL-2, IFN&#947;, and chemokines from activated T cells signal via the phosphoinositide 3-kinase (PI3K), the serine/threonine kinases, Akt and mammalian target of rapamycin (mTOR) pathways. This article reviews the signaling molecules induced by superantigens in the activation of PI3K/Akt/mTOR pathways leading to staphylococcal superantigen-induced toxicity and updates potential therapeutics against superantigens.
authors.affiliation: Department of Immunology, Integrated Toxicology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702, USA. teresa.krakauer@us.army.mil
authors.forename: Teresa
authors.initials: T
authors.lastname: Krakauer
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001427:Bacterial Toxins / Q000276:immunology / Q000633:toxicity*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology / Q000633:toxicity*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D012772:Shock, Septic / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013210:Staphylococcus / Q000737:chemistry*; D018089:Superantigens / Q000276:immunology / Q000633:toxicity*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins; D016207:Cytokines; D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011948:Receptors, Antigen, T-Cell; D018089:Superantigens; D058570:TOR Serine-Threonine Kinases; C030107:enterotoxin F, Staphylococcal; C031818:enterotoxin B, staphylococcal