Toxic shock syndrome pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Pathophysiology
Toxic shock syndrome is known to be caused by intoxication of one of the various exotoxins produced by Staphylococcus aureus, namely Toxic shock syndrome toxin-1 (TSST-1). It may also be caused by Group A streptococcal (GAS) infection. There have been reports of TSS caused by Clostridium sordelli in women undergoing medical abortion.[1][2][3][4][5]
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. [6]The SAg binds through its dodecapeptide region to human epithelial cells, possible CD40 or another unknown receptor, stimulating the production of pro-inflammatory chemokines including TNF-alpha, IL-6 and MIP-3α[7]. 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. [8]. 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.[9]
GAS associated Toxic Shock Syndrome (Toxic shock-like syndrome-TSLS)
Streptococcal strains (particularly those harboring the M protein, specifically M1, M3 and M18) which are capable of producing the super antigens speA, speB and speC have been associated with severe cases of streptococcal toxic shock syndrome (TSLS)[10][11]The pyrogenic exotoxin type A gene is associated with group A streptococcal strains isolated from patients with TSLS and may play a causative role in this illness[12]. SpeA and SpeB non-specifically activate T cells causing release of pro-inflammatory cytokines like IL-6, IL-8, and MIP-3α[13], which leads to fever, rash, capillary leak, and subsequent hypotension, the major symptoms of toxic shock syndrome. Systemic invasion by the GAS is required for producing TSLS, which is in contrast to TSS caused by S.aureus (which only requires mucosal invasion to produce TSS). GAS associated TSS is not tampon-associated, because streptococci are fermentative and thus do not require oxygen for growth and toxin production (unlike S.aureus associated TSS)
References
- ↑ McGregor JA, Soper DE, Lovell G, Todd JK (1989). "Maternal deaths associated with Clostridium sordellii infection". Am. J. Obstet. Gynecol. 161 (4): 987–95. PMID 2801850.
- ↑ "Clostridium sordellii toxic shock syndrome after medical abortion with mifepristone and intravaginal misoprostol--United States and Canada, 2001-2005". MMWR Morb. Mortal. Wkly. Rep. 54 (29): 724. 2005. PMID 16049422.
- ↑ Fischer M, Bhatnagar J, Guarner J, Reagan S, Hacker JK, Van Meter SH, Poukens V, Whiteman DB, Iton A, Cheung M, Dassey DE, Shieh WJ, Zaki SR (2005). "Fatal toxic shock syndrome associated with Clostridium sordellii after medical abortion". N. Engl. J. Med. 353 (22): 2352–60. doi:10.1056/NEJMoa051620. PMID 16319384.
- ↑ Sinave C, Le Templier G, Blouin D, Léveillé F, Deland E (2002). "Toxic shock syndrome due to Clostridium sordellii: a dramatic postpartum and postabortion disease". Clin. Infect. Dis. 35 (11): 1441–3. doi:10.1086/344464. PMID 12439811.
- ↑ Ho CS, Bhatnagar J, Cohen AL, Hacker JK, Zane SB, Reagan S, Fischer M, Shieh WJ, Guarner J, Ahmad S, Zaki SR, McDonald LC (2009). "Undiagnosed cases of fatal Clostridium-associated toxic shock in Californian women of childbearing age". Am. J. Obstet. Gynecol. 201 (5): 459.e1–7. doi:10.1016/j.ajog.2009.05.023. PMID 19628200.
- ↑ 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.
- ↑ Brosnahan AJ, Schlievert PM (2011). "Gram-positive bacterial superantigen outside-in signaling causes toxic shock syndrome". FEBS J. 278 (23): 4649–67. doi:10.1111/j.1742-4658.2011.08151.x. PMC 3165073. PMID 21535475.
- ↑ 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.
- ↑ Goshorn SC, Schlievert PM (1989). "Bacteriophage association of streptococcal pyrogenic exotoxin type C". J. Bacteriol. 171 (6): 3068–73. PMC 210016. PMID 2566595.
- ↑ Stevens DL, Tanner MH, Winship J, Swarts R, Ries KM, Schlievert PM, Kaplan E (1989). "Severe group A streptococcal infections associated with a toxic shock-like syndrome and scarlet fever toxin A". N. Engl. J. Med. 321 (1): 1–7. doi:10.1056/NEJM198907063210101. PMID 2659990.
- ↑ Hauser AR, Stevens DL, Kaplan EL, Schlievert PM (1991). "Molecular analysis of pyrogenic exotoxins from Streptococcus pyogenes isolates associated with toxic shock-like syndrome". J. Clin. Microbiol. 29 (8): 1562–7. PMC 270163. PMID 1684795.
- ↑ Llewelyn M, Cohen J (2002). "Superantigens: microbial agents that corrupt immunity". Lancet Infect Dis. 2 (3): 156–62. PMID 11944185.