Department of Microbiology and Immunology, Institute of Biomedicine, and Mucosal Immunobiology and Vaccine Center, University of Gothenburg, Gothenburg, Sweden.
Innate Immun. 2011 Apr;17(2):191-203. doi: 10.1177/1753425909357970. Epub 2010 Feb 3.
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.
幽门螺杆菌在人类胃黏膜中引起慢性炎症，其特征是干扰素-γ（IFN-γ）的产生增加。人类胃黏膜中存在自然杀伤（NK）细胞，并且 NK 细胞能够产生 IFN-γ，这表明 NK 细胞在针对 H. pylori 感染的免疫反应中起重要作用。由于 NK 细胞以前已经显示出对细菌成分产生 IFN-γ的反应，因此我们研究了识别 H. pylori 的机制。我们发现抑制 MyD88 同源二聚体化导致 IFN-γ产生减少，并且抑制 p38 MAPK 减少了 IFN-γ的产生和分泌。进一步的研究表明，Toll 样受体（TLR），特别是 TLR2 参与其中。最后，我们表明 H. pylori 特异性膜结合脂蛋白 HpaA 通过 TLR2 的识别诱导 NK 细胞产生 IFN-γ。总之，我们建议 TLR2 参与人类 NK 细胞对 H. pylori 的识别，并且 HpaA 是识别的重要 TLR2 配体。
