梅毒的发病机制

Pathogenesis of Syphilis

梅毒是梅毒螺旋体(TP)感染引起的一个复杂的、涉及多个脏器的慢性感染性疾病。临床表现多样,可分为显性梅毒和潜伏梅毒。TP通过破损皮肤和黏膜传播,几个小时后可以到达附近淋巴结和内脏器官。由于体外不能培养,发病机制和宿主与病原体之间的相互作用只能有限地来自于动物模型。持续感染、侵犯神经系统和通过胎盘传播的机理尚不清楚。病原体与宿主免疫应答的相互作用在梅毒发病机制中起重要作用,梅毒螺旋体入侵机体即刻被单核细胞TLR-2识别,并参与固有免疫应答。随后,针对TP表面分子的Ig M和Ig G抗体大量产生,并形成多种多样梅毒皮损。Tpr K基因序列的异质性和多变性与免疫逃逸和免疫耐受有关。早期梅毒以Th1介导的细胞免疫应答为主,晚期Th1/Th2动态平衡向Th2方向飘移,最终导致病原体不能被完全清除。

Syphilis is a complex systemic illness with protean clinical manifestations caused by the spirochete Treponema pallidum. It＇s also a chronic systemic infection that progresses through active and latent stages. Understanding of disease pathogenesis and how host-pathogen interactions influence the course of disease have been compromised by the facts that the organism cannot be grown in vitro and,as an exclusively human pathogen,inferences made from animal models are of limited applicability. Many ques-tions remain about how T. pallidum biology contributes to distinctive features of syphilis,such as its ability to persist in the presence of a brisk host response or its propensity for neuro-invasion and congenital transmission. The interaction between pathogen and host immune response plays a important role in pathogenesis of syphilis. Toll-like receptor（ TLR）-2 has been shown to recognize T. pallidum microbial patterns and is involved in mediating the innate response. Also humoral responses consisting of Ig M and Ig G antibodies are detected post-infection and are specific for a broad range of T.pallidum surface molecules. These antibodies have been shown to have opsonizing activity as well as the ability to immobilize the organisms and neutralize their ability to form lesions. However the pathogen uses antigenic variation mechanism to avoid adaptive immune response. Tpr K gene,which belongs to one of the sub-family of Treponema pallidum repeat protein family genes（ Tpr） has been shown increasing sequence variation in response to immune pressure,which may have a function in immune evasion. Antigenic variation through gene conversion has been hypothesized to be one mechanism of escaping immune surveillance,allowing for prolonged infection and persistence in the presence of a robust host response. Furthermore,Human and animal studies also suggest that a Th1 response is elicited in primary syphilis. Progression to the secondary stage is accompanied by a shift to a Th2 response,allowing for incomplete clearance of the pathogen.