Toxic shock syndrome pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Pathophysiology
In both TSS (caused by S. aureus) and TSLS (caused by S. pyogenes), disease progression stems from a superantigen toxin that allows the non-specific binding of MHC II with T cell receptors, resulting in polyclonal T-cell activation. TSS due to Clostridium sordelli has also been identified in women undergoing medical abortion.
TSST-1 associated Toxic shock syndrome
TSST-1 associated Toxic Shock Syndrome. A protein based exotoxin, called toxic shock syndrome toxin-1 (TSST-1), which acts as a superantigen (SAg) has been identified that is associated with strains of S. aureus isolated from patients with TSS. SAgs bind to certain regions of major histocompatibility complex (MHC) class II molecules of antigen-presenting cells (APCs) outside the traditional antigen-binding site and at the same time bind in their native form to T cells at specific motifs of the variable region of the beta chain (Vbeta) of the T cell receptor (TcR). This interaction triggers the activation (proliferation) of the targeted T lymphocytes and leads to release of high amounts of various cytokines and other effectors by immune cells. [1]The SAg binds through its dodecapeptide region to human epithelial cells, possible CD40 or another unknown receptor, stimulating the production of pro-inflammatory chemokines. Small amounts of cytolysins, particularly α-toxin, are required to facilitate this process through combinations of their cytotoxic and pro-inflammatory properties. The SAg must penetrate the mucosal barrier to cause disease, but it appears likely that submucosal SAg activities, rather than systemic activities, are sufficient for TSS production. [2]. SAgs cause release of IL-1 beta and IL-6 from antigen presenting cells (APC) and have a direct action on the hypothalamic temperature control center. Staphylococcal toxic shock syndrome toxin 1 (TSST-1) is also the cause of menstrual toxic shock syndrome (mTSS) associated with vaginal colonization by Staphylococcus aureus; IL-8 and MIP-3α, may originate from vaginal epithelial cells, which are highly chemotactic.[3]
References
- ↑ Alouf JE, Müller-Alouf H (2003). "Staphylococcal and streptococcal superantigens: molecular, biological and clinical aspects". Int. J. Med. Microbiol. 292 (7–8): 429–40. doi:10.1078/1438-4221-00232. PMID 12635926.
- ↑ Stach CS, Herrera A, Schlievert PM (2014). "Staphylococcal superantigens interact with multiple host receptors to cause serious diseases". Immunol. Res. 59 (1–3): 177–81. doi:10.1007/s12026-014-8539-7. PMC 4125451. PMID 24838262.
- ↑ Schlievert PM, Nemeth KA, Davis CC, Peterson ML, Jones BE (2010). "Staphylococcus aureus exotoxins are present in vivo in tampons". Clin. Vaccine Immunol. 17 (5): 722–7. doi:10.1128/CVI.00483-09. PMC 2863369. PMID 20335433.