Interferon-gamma secretion is induced in IL-12 stimulated human NK cells by recognition of Helicobacter pylori or TLR2 ligands.
Helicobacter pylori induce a chronic inflammation in the human gastric mucosa characterized by increased production of interferon-gamma (IFN-γ). The presence of natural killer (NK) cells in the human gastric mucosa and the ability of NK cells to produce IFN-γ suggest an important role of NK cells in the immune response directed towards H. pylori infection. Since NK cells previously have been shown to respond to bacterial components with IFN-γ production, we investigated the mechanisms for the recognition of H. pylori. We found that inhibition of MyD88 homodimerization resulted in decreased production of IFN-γ and that inhibition of the p38 MAPK decreased the production as well as the secretion of IFN-γ. Further studies indicated an involvement of Toll-like receptors (TLRs), in particular TLR2. Finally, we showed that the H. pylori specific membrane bound lipoprotein HpaA induced IFN-γ production from NK cells through recognition by TLR2. In conclusion, we suggest an involvement of TLR2 in the recognition of H. pylori by human NK cells and that HpaA is a TLR2 ligand important for recognition.
Department of Microbiology and Immunology, Institute of Biomedicine, and Mucosal Immunobiology and Vaccine Center, University of Gothenburg, Gothenburg, Sweden. asa.lindgren@microbio.gu.se
Asa
A
Lindgren
Voja
V
Pavlovic
Carl-Fredrik
CF
Flach
Asa
A
Sjöling
Samuel
S
Lundin
D018829:Adhesins, Bacterial / Q000276:immunology / Q000378:metabolism*; D005753:Gastric Mucosa / Q000276:immunology* / Q000382:microbiology; D005786:Gene Expression Regulation / Q000276:immunology; D016481:Helicobacter Infections / Q000276:immunology* / Q000382:microbiology; D016480:Helicobacter pylori / Q000276:immunology* / Q000472:pathogenicity; D054884:Host-Pathogen Interactions; D006801:Humans; D007249:Inflammation; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D053594:Myeloid Differentiation Factor 88 / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
D018829:Adhesins, Bacterial; D008024:Ligands; D053594:Myeloid Differentiation Factor 88; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; C095977:adhesin A, Helicobacter; D018664:Interleukin-12; D048051:p38 Mitogen-Activated Protein Kinases