Title MINIREVIEW] Shiga Toxins Expressed by Human Pathogenic Bacteria Induce Immune Responses in Host Cells
Author Moo-Seung Lee1*, Myung Hee Kim1, and Vernon L. Tesh2
Address 1Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea, 22Department of Microbial and Molecular Pathogenesis, Room 3002, Medical Research and Education Building College of Medicine, Texas A&M Health Science Center, 8447 State Highway 47 Bryan, TX 77807-1359, USA
Bibliography Journal of Microbiology, 51(6),724–730, 2013,
DOI 10.1007/s12275-013-3429-6
Key Words inflammatory response, Shiga toxin, signaling, HUS, animal model
Abstract Shiga toxins are a family of genetically and structurally related toxins that are the primary virulence factors produced by the bacterial pathogens Shigella dysenteriae serotype 1 and certain Escherichia coli strains. The toxins are multifunctional proteins inducing protein biosynthesis inhibition, ribotoxic and ER stress responses, apoptosis, autophagy, and inflammatory cytokine and chemokine production. The regulated induction of inflammatory responses is key to minimizing damage upon injury or pathogen-mediated infections, requiring the concerted activation of multiple signaling pathways to control cytokine/chemokine expression. Activation of host cell signaling cascades is essential for Shiga toxinmediated proinflammatory responses and the contribution of the toxins to virulence. Many studies have been reported defining the inflammatory response to Shiga toxins in vivo and in vitro, including production and secretion of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), macrophage inflammatory protein-1α/β (MIP-1α/β), macrophage chemoattractant monocyte chemoattractant protein 1 (MCP-1), interleukin 8 (IL-8), interleukin 6 (IL-6), and Groβ. These cytokines and chemokines may contribute to damage in the colon and development of life threatening conditions such as acute renal failure (hemolytic uremic syndrome) and neurological abnormalities. In this review, we summarize recent findings in Shiga toxin-mediated inflammatory responses by different types of cells in vitro and in animal models. Signaling pathways involved in the inflammatory responses are briefly reviewed.