Enterotoxins: Microbial Proteins and Host Cell Dysregulation

The special issue “Enterotoxins: Microbial Proteins and Host Cell Dysregulation” is comprised of research articles and reviews covering a diverse group of toxins that affect the gut and dysregulate host immune response in mechanistically different ways. Excellent in-depth reviews of staphylococcal superantigens and Clostridium perfringens toxins are the cornerstones of this issue. The present editorial highlights these papers grouped by toxin class and within each toxin class papers are discussed in order of publication date, with reviews appearing first, followed by original articles. The review entitled “Update on staphylococcal superantigen-induced signaling pathways and therapeutic interventions” gives a comprehensive review of signaling pathways induced by staphylococcal superantigens and evaluations of therapeutics targeting these pathways [1]. Of great interest is the presentation of pathways engaged by these bacterial superantigens, an extensive list of effective and ineffective therapies, as well as the benefits associated with specific targeting of activated molecules and pathways. A detailed pathway diagram of signaling molecules and points of intervention by specific inhibitors is available to readers. Another information-rich review, “Soluble T cell receptor Vβ domains engineered for high-affinity binding to staphylococcal or streptococcal superantigens”, presents a brief review of the structure and sequence homology of multiple superantigens produced by Staphylococcus aureus and group A Streptococcus [2]. The different modes of binding of these superantigens to both major histocompatibility complex (MHC) class II and variable regions of T cell receptor beta chain (TCR Vβ) are presented, including the targeting of specific epitopes on superantigens with high affinity TCR Vβ mutants. A flow chart and schematic of yeast display methodology illustrate techniques used in the engineering of these soluble high affinity TCR Vβ domains against superantigens. The interaction of each specific high affinity Vβ domain against the superantigens SEA, SEB, SEC3, TSST-1, SpeA, and SpeC is displayed by their co-crystal structures. Of great interest to the scientific community is the utility of these high affinity TCR Vβ domains in blocking superantigen-induced lethality and preventing necrotizing pneumonia induced by SEC secreting methicillin-resistant S. aureus in various rabbit models of disease. The review article “Staphylococcal enterotoxins in the etiopathogenesis of mucosal autoimmunity within the gastrointestinal tract” addresses the immunopathogenic effects of staphylococcal enterotoxins in the gastrointestinal tract [3]. Different immune cell types, Th1, Th2, Th17 and regulatory T cells, participating in gut immune defense and tolerance are described. The early activation of specific Vβ T cells in blood and lymphoid organs results in induction of proinflammatory mediators (IL-1β, IL-2, IL-6, IL-8, MCP-1, IFNγ and TNFα) eliciting inflammatory cell infiltration to the gastrointestinal tract and the proliferation of T cells in lymphoid organs. SEB also directly reduces mucosal tight-junction proteins and, together with SEB-induced inflammatory cytokines, destroys epithelial barriers in the intestine, thus initiating pathological effects. The histochemical presentation