title: Inflammasome Activation by Helicobacter pylori and Its Implications for Persistence and Immunity.
abstract: Infection with the Gram-negative pathogen Helicobacter pylori is the most prevalent chronic bacterial infection affecting about 50 % of the human world population and is the main risk factor for gastric cancer development. The pro-inflammatory cytokine IL-1β plays a crucial role in the development of gastric tumors, and polymorphisms in the IL-1 gene cluster resulting in increased IL-1β production have been associated with increased risk for gastric cancer. Recently, Helicobacter pylori was postulated to activate the inflammasome in human and mouse immune cells, and the molecular mechanisms and the bacterial virulence factors activating the inflammasome were elucidated in cell culture as well as animal models. It appears that H. pylori-induced IL-1β secretion is mediated by activation of toll-like receptor 2 (TLR-2), Nod-like receptor family member NLRP3 and caspase-1. The cag pathogenicity island-encoded type IV secretion system, lipopolysaccharide, vacuolating cytotoxin, and urease B subunit appear to play a role in inflammasome activation. In addition, recent results indicate that the TLR-2 → NLRP3 → caspase-1 → IL-18 axis is critical to H. pylori-specific immune regulation conferring protection against allergen-induced asthma and inflammatory bowel disease in murine models. The present chapter will review the proposed mechanisms of NLRP3 inflammasome activation during H. pylori infection and discuss the recent progress in this important research field.
authors.affiliation: Department of Biology, Division of Microbiology, Friedrich Alexander University Erlangen-Nuremberg, Staudtstrasse 5, 91085, Erlangen, Germany.
authors.forename: Suneesh Kumar
authors.initials: SK
authors.lastname: Pachathundikandi
authors.affiliation: Institute of Molecular Cancer Research, University of Zürich, Winterthurerstr. 190, 8057, Zurich, Switzerland.
authors.forename: Anne
authors.initials: A
authors.lastname: Müller
authors.affiliation: Department of Biology, Division of Microbiology, Friedrich Alexander University Erlangen-Nuremberg, Staudtstrasse 5, 91085, Erlangen, Germany. steffen.backert@fau.de.
authors.forename: Steffen
authors.initials: S
authors.lastname: Backert
mesh_terms: D000818:Animals; D016481:Helicobacter Infections / Q000276:immunology* / Q000382:microbiology*; D016480:Helicobacter pylori / Q000276:immunology* / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D058847:Inflammasomes / Q000235:genetics / Q000276:immunology*; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology
chemical_list: D058847:Inflammasomes; D053583:Interleukin-1beta
keywords: Caspase; Cytokine; Inflammasome; LPS; NOD-like receptor; Pyroptosis; Toll-like receptor; Type IV secretion; Urease