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 Vβ 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 α, interleukin 1 (IL-1), IL-2, interferon γ (IFNγ), 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 NFκB activation. Independently, IL-2, IFNγ, 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.
Highlights
Staphylococcus aureus is a ubiquitous gram-positive coccus that produces several exotoxins with potent immunostimulating activities which contribute to its ability to cause disease in humans, most notably food poisoning, toxic shock, and autoimmune diseases [1,2,3,4,5,6,7]
Tumor necrosis factor α (TNFα) binds to TNF receptor 1 (TNFR1), TNFR2 and both receptors use intracellular TRAFs different from those used by IL-1 receptor 1 (IL-1R1) or toll-like receptors (TLRs) but activating NFκB, resulting in expression of other cytokines, adhesion and co-stimulatory molecules [21,92]
Bi-specific chimeric inhibitors composed of the DRα1 domain of major histocompatibility complex (MHC) class II and Vβ domain of the T cell receptor (TCR) connected by a flexible GSTAPPA)2 linker were reported to bind staphylococcal enterotoxin B (SEB) competitively and prevent its binding to MHC class II of antigen-presenting cells (APC) and TCR on T
Summary
Staphylococcus aureus is a ubiquitous gram-positive coccus that produces several exotoxins with potent immunostimulating activities which contribute to its ability to cause disease in humans, most notably food poisoning, toxic shock, and autoimmune diseases [1,2,3,4,5,6,7]. Superantigen binds outside the peptide-binding groove of the major histocompatibility complex (MHC) class II and bypasses conventional antigen processing by antigen-presenting cells (APC) [3,7,8]. By interacting with both MHC class II molecules on APC and specific elements within the variable region of the Vβ chains of the T cell receptor (TCR), these microbial toxins perturb the immune system and induce high levels of proinflammatory cytokines and chemokines [9,10,11,12,13,14,15,16]. Because it is common to encounter pathogens and their toxins concomitantly in real life, superantigens can have profound toxic effects at extremely low concentrations
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call