Wang Yang, Liu Suli, Li Yuan, Wang Qi, Shao Jiari, Chen Ying, Xin Jiuqing
National Contagious Bovine Pleuropneumonia Reference Laboratory, Division of Bacterial Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, CAAS, Harbin, 150001, China; Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, College of Bioengineering, Hubei University of Technology, Wuhan, 430068, China.
National Contagious Bovine Pleuropneumonia Reference Laboratory, Division of Bacterial Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, CAAS, Harbin, 150001, China.
Dev Comp Immunol. 2016 Feb;55:111-8. doi: 10.1016/j.dci.2015.10.017. Epub 2015 Oct 23.
Mycoplasma bovis causes pneumonia, otitis media, and arthritis in young calves, resulting in economic losses to the cattle industry worldwide. M. bovis pathogenesis results in part from excessive immune responses. Lipid-associated membrane proteins (LAMPs) can potently induce host innate immunity. However, interactions between M. bovis-derived LAMPs and Toll-like receptors (TLRs), or signaling pathways eliciting active inflammation and NF-κB activation, are incompletely understood. Here, we found that IL-1β expression was induced in embryonic bovine lung (EBL) cells stimulated with M. bovis-derived LAMPs. Subcellular-localization analysis revealed nuclear p65 translocation following EBL cell stimulation with M. bovis-derived LAMPs. An NF-κB inhibitor reversed M. bovis-derived LAMP-induced IL-1β expression. TLR2 and myeloid differentiation primary response gene 88 (MyD88) overexpression increased LAMP-dependent IL-1β induction. TLR2-neutralizing antibodies reduced IL-1β expression during LAMP stimulation. LAMPs also inhibited IL-1β expression following overexpression of a dominant-negative MyD88 protein. These results suggested that M. bovis-derived LAMPs activate IL-1β production through the NF-κB pathway via TLR2 and MyD88.
牛支原体可导致犊牛发生肺炎、中耳炎和关节炎，给全球养牛业造成经济损失。牛支原体发病机制部分源于过度的免疫反应。脂质相关膜蛋白（LAMPs）可有效诱导宿主固有免疫。然而，牛支原体来源的LAMPs与Toll样受体（TLRs）之间的相互作用，或引发活性炎症和NF-κB激活的信号通路，目前尚未完全明确。在此，我们发现用牛支原体来源的LAMPs刺激胚胎牛肺（EBL）细胞可诱导白细胞介素-1β（IL-1β）表达。亚细胞定位分析显示，用牛支原体来源的LAMPs刺激EBL细胞后，核p65发生易位。一种NF-κB抑制剂可逆转牛支原体来源的LAMPs诱导的IL-1β表达。Toll样受体2（TLR2）和髓样分化初级反应基因88（MyD88）过表达可增强LAMP依赖的IL-1β诱导作用。TLR2中和抗体可降低LAMP刺激期间的IL-1β表达。在显性负性MyD88蛋白过表达后，LAMPs也可抑制IL-1β表达。这些结果表明，牛支原体来源的LAMPs通过TLR2和MyD88经NF-κB途径激活IL-1β的产生。
