淋病奈瑟菌致病的免疫学机制

Immunological mechanisms of Neisseria gonorrhoeae infection: An update

淋病奈瑟菌作为淋病的病原体,人类是其唯一天然宿主,且普遍易感。淋病奈瑟菌感染后,机体一方面通过募集中性粒细胞等炎症细胞来抵抗其入侵,另一方面也可通过抗原呈递等过程来启动机体适应性免疫应答予以消灭,但淋病奈瑟菌存在一系列免疫逃逸机制,使得感染难以清除。在固有免疫系统中,淋病奈瑟菌可分泌核酸酶分解中性粒细胞外诱捕(NETs)、抑制呼吸爆发来抵抗中性粒细胞的杀伤作用,激活NLRP3炎症小体促进炎症细胞的焦亡,亦可调节巨噬细胞的分化削弱炎症反应,结合H因子来逃避补体介导的杀伤作用。淋病奈瑟菌感染难以产生有效的适应性免疫反应及免疫记忆。淋病奈瑟菌促进转化生长因子β(TGF-β)的产生,从而抑制Th1/Th2细胞介导的适应性免疫反应,可与B细胞表面的CEACAM1结合促进B细胞的凋亡,亦可与T细胞表面的CEACAM1结合抑制辅助性T细胞增生,使得B细胞难以产生高亲和力的特异性抗体。随着淋病奈瑟菌耐药性不断增加,这些免疫学研究对于开发新型疗法及疫苗研制具有重要意义。

Neisseria gonorrhoeae(NG）,as a pathogen of gonorrhea,is strictly limited to growth on the human host. In case of gonococcal infection,the body may recruit such inflammatory cells as neutrophils to resist the invasion of NG or initiate its adaptive immune response by antigen presentation to eliminate the pathogen. However,a series of immune escape mechanisms of NG make it difficult to clear up the infection. In the innate immune system,NG can not only secrete thermonuclease to degrade neutrophile granulocytes,inhibit respiratory burst to resist killing by neutrophils,activate NLRP3 to prompt the pyronecrosis of inflammatory cells,but also regulate the differentiation of macrophages to reduce the inflammatory response,combine with factor H to evade complement-mediated killing. NG infection can hardly give rise to effective adaptive immune response and immune memory,but can promote TGF-β production to inhibit Th1/Th2-mediated adaptive immune response,bind to CEACAM1 on the B cell surface to promote apoptosis in B cells,and combine with CEACAM1 on the T cell surface to inhibit helper T cell proliferation,which makes it difficult for B cells to produce high-affinity specific antibodies. With the increasing drug-resistance of NG,immunological studies may play a significant role in the development of novel therapies and effective vaccines against the infection.