Abstract
Staphylococcal enterotoxin B (SEB) of Staphylococcus aureus, and related superantigenic toxins produced by myriad microbes, are potent stimulators of the immune system causing a variety of human diseases from transient food poisoning to lethal toxic shock. These protein toxins bind directly to specific Vβ regions of T-cell receptors (TCR) and major histocompatibility complex (MHC) class II on antigen-presenting cells, resulting in hyperactivation of 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. Because of superantigen-induced T cells skewed toward TH1 helper cells, and the induction of proinflammatory cytokines, superantigens can exacerbate autoimmune diseases. Upon TCR/MHC ligation, pathways induced by superantigens include the mitogen-activated protein kinase cascades and cytokine receptor signaling, resulting in activation of NFκB and the phosphoinositide 3-kinase/mammalian target of rapamycin pathways. Various mouse models exist to study SEB-induced shock including those with potentiating agents, transgenic mice and an “SEB-only” model. However, therapeutics to treat toxic shock remain elusive as host response genes central to pathogenesis of superantigens have only been identified recently. Gene profiling of a murine model for SEB-induced shock reveals novel molecules upregulated in multiple organs not previously associated with SEB-induced responses. The pivotal genes include intracellular DNA/RNA sensors, apoptosis/DNA damage-related molecules, immunoproteasome components, as well as antiviral and IFN-stimulated genes. The host-wide induction of these, and other, antimicrobial defense genes provide evidence that SEB elicits danger signals resulting in multi-organ damage and toxic shock. Ultimately, these discoveries might lead to novel therapeutics for various superantigen-based diseases.
Highlights
Superantigens and ImmunityStaphylococcus aureus is a Gram-positive coccus and member of the Micrococcaceae family, which includes non-pathogenic genera found in soil, water, and on skin
Specialty section: This article was submitted to Microbial Immunology, a section of the journal Frontiers in Immunology
Staphylococcal enterotoxin B (SEB) of Staphylococcus aureus, and related superantigenic toxins produced by myriad microbes, are potent stimulators of the immune system causing a variety of human diseases from transient food poisoning to lethal toxic shock
Summary
Staphylococcus aureus is a Gram-positive coccus and member of the Micrococcaceae family, which includes non-pathogenic genera found in soil, water, and on skin Both planktonic- and biofilm-based versions of S. aureus can cause disease in an infected host, subsequently becoming (at times) quite difficult to clear from the body [5, 6]. Methicillin was meant to overcome the increasingly prevalent, penicillin-resistant strains of S. aureus first detected during the mid-1940s in hospitals and throughout the community These strains were isolated just 2 years after penicillin’s introduction into clinical practice [27]. Humans (~30%) can be asymptomatic carriers of S. aureus strains that possess virulence factor genes encoding antibiotic resistance, toxins, and other proteins that promote some nasty, potentially fatal diseases [1, 3, 36,37,38,39,40] (Table 1). The risk factors are many for children carrying MRSA nasally, and include [1] 4; [4]
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