Helicobacter pylori targets dendritic cells to induce immune tolerance, promote persistence and confer protection against allergic asthma.
The bacterial pathogen Helicobacter pylori is predominantly known for its tight association with peptic ulcer disease and gastric cancer. However, recent evidence suggests that chronic infection with H. pylori may also be beneficial to the host by conferring protection against allergies, asthma and inflammatory bowel diseases. The protective effects of H. pylori depend on highly suppressive regulatory T-cells. In this addendum, we summarize results showing that H. pylori infection efficiently re-programs dendritic cells (DCs) toward a tolerance-promoting phenotype; their "tolerogenic" activity requires inflammasome activation and the secretion of interleukin-18. H. pylori-experienced DCs fail to induce T-cell effector functions, but efficiently induce FoxP3 expression in naive T-cells in vitro and in vivo. The experimental depletion of DCs breaks tolerance and results in improved infection control, but also in aggravated T-cell-driven immunopathology. In summary, we propose that H. pylori evades adaptive immune responses by re-programming DCs in favor of tolerance over immunity.
Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland.
Mathias
M
Oertli
Anne
A
Müller
D000818:Animals; D001249:Asthma / Q000276:immunology / Q000517:prevention & control; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology*; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D016480:Helicobacter pylori / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000517:prevention & control; D057131:Immune Evasion; D007108:Immune Tolerance; D058847:Inflammasomes / Q000276:immunology; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000517:prevention & control; D020382:Interleukin-18 / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D058847:Inflammasomes; D020382:Interleukin-18