Many people are at increased risk of developing life-threatening extra-intestinal/extra-renal complications, such as hemolytic uremic syndrome (HUS), following infections with Shiga toxin-producing bacteria. Shiga toxins are primary virulence factors produced by Shigella dysenteriae serotype 1 and certain Escherichia coli strains. These toxins are multi-functional proteins that mediate the inhibition of protein synthesis and that activate various host cellular signaling pathways to induce (i) ribotoxic and ER stress responses; (ii) apoptosis; (iii) autophagy, and (iv) inflammatory cytokine and chemokine production. In many instances, the activation of host cell signaling cascades leads to cell death. Inflammatory responses may represent key factors leading to the exacerbation of tissue damage following infection.
Numerous studies have defined host responses to Shiga toxin type 1 (Stx1) and Shiga toxin type 2 (Stx2) in a variety of susceptible cell types in vitro. In mouse and non-human primate models, the administration of Shiga toxins has been extensively demonstrated to elicit immune responses via the production of chemokines and pro-inflammatory cytokines, including tumor necrosis factor alpha (TNF-a) and interleukin-1ß (IL-1ß), that may contribute to renal damage or accelerate lethality of the animals. In patients, there is a strong association between the localized induction of a pro-inflammatory milieu and neurological involvement and impairment of renal function. However, additional studies to improve our understanding of the role of Shiga toxins in renal and neurological immunopathology are needed. Cells involved in innate immunity (neutrophils and monocytes) and other cell types (epithelial cells and endothelial cells) may be activated to produce cytokines/chemokines in response to these toxins. The precise mechanisms of activation of host cell signaling cascades, and the contributions of Shiga toxin-mediated host innate immune response to pathogenesis remain to be characterized. A better understanding of how Shiga toxin-mediated inflammation is regulated, and how the response exacerbates disease progression, is necessary to formulate improved therapies that aim to inhibit host cell death and prevent tissue damage.
In this Research Topic, we would like to welcome the submission of Original Research, Review and Opinion articles, Methods, and Case Reports covering recent advances in our current understanding of the pathogenesis of Shiga toxin-producing Shigella and E.coli (STEC).
Many people are at increased risk of developing life-threatening extra-intestinal/extra-renal complications, such as hemolytic uremic syndrome (HUS), following infections with Shiga toxin-producing bacteria. Shiga toxins are primary virulence factors produced by Shigella dysenteriae serotype 1 and certain Escherichia coli strains. These toxins are multi-functional proteins that mediate the inhibition of protein synthesis and that activate various host cellular signaling pathways to induce (i) ribotoxic and ER stress responses; (ii) apoptosis; (iii) autophagy, and (iv) inflammatory cytokine and chemokine production. In many instances, the activation of host cell signaling cascades leads to cell death. Inflammatory responses may represent key factors leading to the exacerbation of tissue damage following infection.
Numerous studies have defined host responses to Shiga toxin type 1 (Stx1) and Shiga toxin type 2 (Stx2) in a variety of susceptible cell types in vitro. In mouse and non-human primate models, the administration of Shiga toxins has been extensively demonstrated to elicit immune responses via the production of chemokines and pro-inflammatory cytokines, including tumor necrosis factor alpha (TNF-a) and interleukin-1ß (IL-1ß), that may contribute to renal damage or accelerate lethality of the animals. In patients, there is a strong association between the localized induction of a pro-inflammatory milieu and neurological involvement and impairment of renal function. However, additional studies to improve our understanding of the role of Shiga toxins in renal and neurological immunopathology are needed. Cells involved in innate immunity (neutrophils and monocytes) and other cell types (epithelial cells and endothelial cells) may be activated to produce cytokines/chemokines in response to these toxins. The precise mechanisms of activation of host cell signaling cascades, and the contributions of Shiga toxin-mediated host innate immune response to pathogenesis remain to be characterized. A better understanding of how Shiga toxin-mediated inflammation is regulated, and how the response exacerbates disease progression, is necessary to formulate improved therapies that aim to inhibit host cell death and prevent tissue damage.
In this Research Topic, we would like to welcome the submission of Original Research, Review and Opinion articles, Methods, and Case Reports covering recent advances in our current understanding of the pathogenesis of Shiga toxin-producing Shigella and E.coli (STEC).
