Nagashima Hiroyuki, Iwatani Shun, Cruz Modesto, Jiménez Abreu José A, Uchida Tomohisa, Mahachai Varocha, Vilaichone Ratha-Korn, Graham David Y, Yamaoka Yoshio
Department of Environmental and Preventive Medicine Department of Medicine-Gastroenterology, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas.
Institute of Microbiology and Parasitology, Department of Science, Autonomous University of Santo Domingo Department of Biomedical Research, School of Medicine, Santiago Technological University.
J Infect Dis. 2015 Nov 15;212(10):1666-76. doi: 10.1093/infdis/jiv270. Epub 2015 May 14.
Innate immunity plays important roles in the primary defense against pathogens, and epidemiological studies have suggested a role for Toll-like receptor 1 (TLR1) in Helicobacter pylori susceptibility. Microarray analysis of gastric biopsy specimens from H. pylori-positive and uninfected subjects showed that TLR10 messenger RNA (mRNA) levels were upregulated approximately 15-fold in infected subjects; these findings were confirmed by real-time quantitative polymerase chain reaction analysis. Immunohistochemical investigation showed increased TLR10 expression in the gastric epithelial cells of infected individuals. When H. pylori was cocultured with NCI-N87 gastric cells, both TLR10 and TLR2 mRNA levels were upregulated. We compared the ability of TLR combinations to mediate nuclear factor-κB (NF-κB) activation. Compared with other TLR2 subfamily heterodimers, the TLR2/TLR10 heterodimer mediated the greatest NF-κB activation following exposure to heat-killed H. pylori or H. pylori lipopolysaccharide. We conclude that TLR10 is a functional receptor involved in the innate immune response to H. pylori infection and that the TLR2/TLR10 heterodimer functions in H. pylori lipopolysaccharide recognition.
固有免疫在抵御病原体的初级防御中发挥重要作用，流行病学研究表明Toll样受体1（TLR1）在幽门螺杆菌易感性中起作用。对幽门螺杆菌阳性和未感染受试者的胃活检标本进行微阵列分析显示，感染受试者中TLR10信使核糖核酸（mRNA）水平上调约15倍；这些发现通过实时定量聚合酶链反应分析得到证实。免疫组织化学研究显示，感染个体胃上皮细胞中TLR10表达增加。当幽门螺杆菌与NCI-N87胃细胞共培养时，TLR10和TLR2 mRNA水平均上调。我们比较了TLR组合介导核因子κB（NF-κB）激活的能力。与其他TLR2亚家族异二聚体相比，TLR2/TLR10异二聚体在暴露于热灭活的幽门螺杆菌或幽门螺杆菌脂多糖后介导的NF-κB激活作用最强。我们得出结论，TLR10是参与幽门螺杆菌感染固有免疫反应的功能性受体，且TLR2/TLR10异二聚体在幽门螺杆菌脂多糖识别中发挥作用。
