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Review
. 2019 Mar 23;11(3):178.
doi: 10.3390/toxins11030178.

Staphylococcal Superantigens: Pyrogenic Toxins Induce Toxic Shock

Teresa Krakauer  1
Affiliations
Review

Staphylococcal Superantigens: Pyrogenic Toxins Induce Toxic Shock

Teresa Krakauer. Toxins (Basel). .

Abstract

Staphylococcal enterotoxin B (SEB) and related superantigenic toxins produced by Staphylococcus aureus are potent activators of the immune system. These protein toxins bind to major histocompatibility complex (MHC) class II molecules and specific Vβ regions of T-cell receptors (TCRs), resulting in the activation of both monocytes/macrophages and T lymphocytes. The bridging of TCRs with MHC class II molecules by superantigens triggers an early "cytokine storm" and massive polyclonal T-cell proliferation. Proinflammatory cytokines, tumor necrosis factor α, interleukin 1 (IL-1), IL-2, interferon γ (IFNγ), and macrophage chemoattractant protein 1 elicit fever, inflammation, multiple organ injury, hypotension, and lethal shock. Upon MHC/TCR ligation, superantigens induce signaling pathways, including mitogen-activated protein kinase cascades and cytokine receptor signaling, which results in NFκB activation and the phosphoinositide 3-kinase/mammalian target of rapamycin pathways. In addition, gene profiling studies have revealed the essential roles of innate antimicrobial defense genes in the pathogenesis of SEB. The genes expressed in a murine model of SEB-induced shock include intracellular DNA/RNA sensors, apoptosis/DNA damage-related molecules, endoplasmic reticulum/mitochondrial stress responses, immunoproteasome components, and IFN-stimulated genes. This review focuses on the signaling pathways induced by superantigens that lead to the activation of inflammation and damage response genes. The induction of these damage response genes provides evidence that SEB induces danger signals in host cells, resulting in multiorgan injury and toxic shock. Therapeutics targeting both host inflammatory and cell death pathways can potentially mitigate the toxic effects of staphylococcal superantigens.

Keywords: SEB; damage response; inflammation; staphylococcal superantigens; therapeutics; toxic shock.

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Conflict of interest statement

The author declares no conflicts of interest.

Figures

Figure 1
Figure 1
Superantigen-activated T-cell signaling pathways and sites of action of FDA-approved immunosuppressants. Abbreviations used: AP1, activating protein 1; CTLA4-Ig, cytotoxic T lymphocyte antigen-4 immunoglobulin; ERK1/2, extracellular signal-regulated kinase 1 and 2; IKK, IκB kinase; IL-2R, interleukin 2 receptor; JNK, jun-N-terminal kinase; MHC II, major histocompatibility complex class II; MAP, mitogen-activated protein kinase; mTORC1, mammalian target of rapamycin complex 1; NFAT, nuclear factor of activated T-cells; NFκB, nuclear factor kappa B; PI3K, phosphoinositide 3 kinase; PKC, protein kinase C; PLCγ, phospholipase C γ; PTK, protein tyrosine kinases; ROS, reactive oxygen species; Treg, regulatory T-cells; TCR, T-cell receptor.
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