title: Helicobacter pylori activates the TLR2/NLRP3/caspase-1/IL-18 axis to induce regulatory T-cells, establish persistent infection and promote tolerance to allergens.
abstract: The Gram-negative bacterium Helicobacter pylori is both a normal constituent of the human gastric microbiota as well as a pathogen tightly associated with severe gastric disorders. The ability of H. pylori to activate the inflammasome and caspase-1 in antigen-presenting and other cells, and the resulting processing and release of caspase-1-dependent cytokines, impacts both the immunomodulatory and pathogenic activities of H. pylori. This article summarizes recent insights by us and others on the bacterial and host prerequisites of inflammasome activation. H. pylori predominantly activates the NLRP3 inflammasome through a process that requires TLR2-dependent licensing. We identified the urease enzyme, a colonization determinant known to be required for acid adaptation, as critically required for activation of the TLR2/NLRP3/caspase-1 axis. The phenotypes of urease mutants, as well as mouse strains defective for TLR2 or NLRP3, are discussed with respect to their ability to support persistent colonization, immune tolerance and immunity to H. pylori.
authors.affiliation: a Institute of Molecular Cancer Research; University of Zurich ; Zurich , Switzerland.
authors.forename: Katrin N
authors.initials: KN
authors.lastname: Koch
authors.affiliation: a Institute of Molecular Cancer Research; University of Zurich ; Zurich , Switzerland.
authors.forename: Anne
authors.initials: A
authors.lastname: Müller
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D002352:Carrier Proteins / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D016481:Helicobacter Infections / Q000276:immunology* / Q000378:metabolism; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D058847:Inflammasomes; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D002352:Carrier Proteins; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D020170:Caspase 1
keywords: Nod-like receptors; allergic diseases; gastrointestinal microbiota; microbial immunomodulation; pro-inflammatory cytokines; regulatory T-cells; toll-like receptors; transposon mutagenesis