分枝杆菌肝素结合血凝素研究进展

结核病是由分枝杆菌感染引起的世界范围内流行的人畜共患病。肝素结合血凝素(heparin-binding adhesin,HBHA)是分枝杆菌表达的一种蛋白质,致病性分枝杆菌的HBHA蛋白具有黏附上皮细胞、扩散感染范围等功能。其发挥黏附功能的C端结构域能够刺激机体产生有效的Th1细胞免疫反应;HBHA特异的黏膜免疫反应能够提供一定的保护效果。这提示HBHA具有制作为疫苗的潜力。而且,HBHA蛋白在活动性结核病患者和潜伏感染者中引发的免疫反应存在差异,这使其可以成为新的诊断抗原。此外,在细胞水平上,HBHA可以利用补体系统进入巨噬细胞,促使巨噬细胞向M1极化,同时能够逃避自噬并诱发线粒体损伤和内质网应激介导功能,这为结核病的致病机制提供了更多的解释。HBHA与宿主之间相互作用认识的积累,可以为HBHA的应用性研究提供依据。

A review of researches on heparin-binding adhesions of Mycobacteria

Tuberculosis is a worldwide zoonosis caused by mycobacteria.Heparin-binding adhesin(HBHA)is a protein produced by mycobacteria,with which the pathogenic strains can attach to epithelium cells and be disseminated to extra-pulmonary organs from lungs.The C terminal domain of it can induce Th1 responses of the body efficiently and a certain level of mucosal immune responses,suggesting its potential for developing a vaccine.Furthermore,the HBHA-specific immune responses in active tuberculosis patients differentiate from that in latent tuberculosis patients which indicates that it may work as a diagnostic antigen.At cellular level,HBHA can intrude into macrophages through complement receptors and turn them to M1 state while escaping from autophagy and triggering mitocondrial damage and endoplasmic reticulum stress.All of these provides more explanations for pathogenesis of tuberculosis.The constantly updated understanding of the interactions between HBHA and the host will provide inspirations for the application study of exploiting its immunogenic potential.