微颗粒介导HPV感染巨噬细胞的研究—尖锐湿疣复发与免疫逃逸的新途径

项目名称： 微颗粒介导HPV感染巨噬细胞的研究—尖锐湿疣复发与免疫逃逸的新途径

项目编号： No.81472000

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 曹育春

作者单位： 华中科技大学

项目金额： 62万元

中文摘要： 最新研究表明，细胞在激活或凋亡时能够释放微颗粒，它可作为载体将包括病毒成分在内的生物活性分子在细胞间转移；研究还发现，微颗粒能被巨噬细胞摄取，其摄取后不被吞噬-溶酶体所清除。课题组前期从尖锐湿疣（CA）组织中分离到微颗粒，并且观察到CA组织中存在较多巨噬细胞，其在体外与消化的CA组织上清孵育可导致HPV感染，提示微颗粒可能作为载体介导HPV感染巨噬细胞。基于上述分析，本项目假设：CA组织能产生包裹HPV的微颗粒，并介导HPV感染巨噬细胞，一方面在巨噬细胞内合成新的HPV形成持续感染，另一方面HPV感染教育巨噬细胞向M2型发展，促进HPV感染的免疫逃逸。本课题以微颗粒为切入点，从CA组织中分离微颗粒与巨噬细胞共培养，对微颗粒介导HPV感染人巨噬细胞的过程及其抗HPV功能的转变展开深入研究，并探讨其内在机制。这将从巨噬细胞的角度阐述CA新的免疫逃逸途径，同时也将揭示CA高复发率的另一可能原因。

中文关键词： 微颗粒；人乳头瘤病毒；巨噬细胞；尖锐湿疣；免疫逃逸

英文摘要： Recent studies highlighted that cells during activation or apoptosis released circular membrane fragments called microparticles(MPs), which were capable of transferring bioactive molecules, including viral components, from one cell to another. Further Studies showed that MPs uptaken by macrophages would not be eliminated via phagolysosome patheway. In preliminary study, our team have isolated MPs from digested warts of condylomata acuminata (CA) and observed local accumulation of macrophages in CA，then we found that HPV could infect macrophages in vitro via co-culture with supernatants of fresh genital warts after digestion. These datas together revealed that MPs might act as vehicles and mediate HPV infection of macrophages. Thus, in this study, we hypothesized that (1) genital warts released MPs containing HPV and MPs mediated HPV infection of macrophages; (2) the infected macrophages could produce new HPV and form persistent infection, in turn, HPV could promote macrophages transformation into M2 type and facilitate immune evasion of viral infection. This study focuses on MPs and tries to elucidate the pathway macrophages infected by HPV and the anti-HPV function changes after that，via isolating MPs from CA warts and co-culture with macrophages. The expected fingdings might provide novel understanding about mechanisms of CA immune evasion and also reason of high recurrent rate of CA at macrophage aspect.

英文关键词： microparticles;human papillomavirus;macrophages;condyloma accuminata;immune evasion