Toxic Shock Syndrome and Bacterial Superantigens: An Update

Abstract

Toxic shock syndrome (TSS) is an acute onset illness characterized by fever, rash formation, and hypotension that can lead to multiple organ failure and lethal shock, as well as desquamation in patients that recover. The disease is caused by bacterial superantigens (SAGs) secreted from Staphylococcus aureus and group A streptococci. SAGs bypass normal antigen presentation by binding to class II major histocompatibility complex molecules on antigen-presenting cells and to specific variable regions on the beta-chain of the T-cell antigen receptor. Through this interaction, SAGs activate T cells at orders of magnitude above antigen-specific activation, resulting in massive cytokine release that is believed to be responsible for the most severe features of TSS. This review focuses on clinical and epidemiological aspects of TSS, as well as important developments in the genetics, biochemistry, immunology, and structural biology of SAGs. From the evolutionary relationships between these important toxins, we propose that there are five distinct groups of SAGs.

Human Leukocyte Antigen Class II Transgenic Mouse Model Unmasks the Significant Extrahepatic Pathology in Toxic Shock Syndrome

“…Exposure to SAgs that are either preformed (as in intentional exposure following attacks with biological weapons containing SAgs) or produced in vivo after bacterial infection can cause potent immune activation. In certain conditions, this immune activation can be robust, leading to a severe systemic cytokine storm (eg, TSS, Kawasaki disease, and neonatal TSS-like exanthematous disease 4,10,11 ). While SIRS leads to MODS and death, in the absence of prompt intervention, 3 the immunopathogenesis of this process is poorly understood because of lack of a robust animal model.…”

“…TSS can be either menstrual or nonmenstrual. 11 The incidence of menstrual TSS is declining worldwide as a result of discontinuation of the tampons associated with it and increased awareness among tampon users. However, menstrual TSS continues to be a significant health concern.…”

“…31 As a result, SIRS induced by SAgs is substantially subdued in conventional mice, rendering them resistant to TSS. 11,31 Therefore, conventional mice are artificially made susceptible to TSS by using sensitizing agents such as D-galactosamine (D-galN), actinomycin, or lipopolysaccharide. 32 D-galN, the commonly used sensitizing agent for inducing TSS, is extremely toxic even when administered alone, 33 and induces liver injury mimicking viral hepatitis.…”

Glycerol Monolaurate Inhibits the Effects of Gram-Positive Select Agents on Eukaryotic Cells

“…Gram positive bacteria produce a large number of human diseases, with TSS and necrotizing pneumonia caused by S. aureus (1,53), pharyngitis and TSS with necrotizing fasciitis induced by group A streptococci (3,54,55), and cutaneous, gastrointestinal, and inhalation anthrax caused by B. anthracis (56). Many of these diseases initiate at mucosal surfaces and occur due to the action of exotoxins on the cells of human hosts.…”

“…Some effects are immunostimulatory, such as superantigen exotoxins, which stimulate T lymphocytes and macrophages to cause toxic shock syndrome (1,3,4). Superantigens are defined by their capacities to induce proliferation of T cells as a function of the β chain variable region of the T cell receptor complex, that causes release of interleukin 2 (IL-2), tumor necrosis factor β (TNF-β), and interferon γ (IFN-γ) (1,4). In concert with activation of T cells is the release of interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) from macrophages (1,4).…”