NETs在眼内抑制HIV感染视网膜小胶质细胞的作用机制

研究发现HIV患者眼内液中有较高HIV病毒载量，视网膜小胶质细胞被证实是眼内HIV感染、复制释放的主要靶细胞，所以抑制眼内HIV感染小胶质细胞是清除眼内HIV的可能途径。中性粒细胞释放的NETs能够捕获HIV病毒颗粒、降低HIV感染力；我们预实验发现HIV患者视网膜组织中有NETs共定位在小胶质细胞上，NETs在体外可以抑制HIV感染视网膜小胶质细胞。据此我们推测：眼内HIV诱导NETs生成，NETs在眼内捕获HIV病毒颗粒、抑制HIV感染小胶质细胞。所以本课题预通过分析HIV患者眼内液和视网膜组织中HIV与NETs表达量的关系，寻找视网膜组织中NETs捕获HIV病毒颗粒的证据，证实NETs在眼内对HIV的作用；同时通过体外细胞实验研究NETs抑制HIV感染视网膜小胶质细胞的机制。预探讨NETs在眼内抗HIV的可能途径，为抑制甚至清除眼内HIV提供理论依据。

It’s reported that there is a high level of HIV load in the intraocular fluid of HIV patients. Retinal microglia has been confirmed to be the main target of HIV infection, and is the reservoir for HIV replication in the eye. Therefore, inhibition of HIV infecting microglia becomes a possible way to eliminate intraocular HIV. Surprisingly, it has been confirmed that NETs released by neutrophils can capture HIV particles and inhibit HIV infectivity. Meanwhile, our preliminary experiment found that NETs deposit near microglia among the retina of HIV patients, and NETs can inhibit HIV infecting microglia in vitro. Therefore, we speculate that neutrophils release NETs under the induction of intraocular HIV, then NETs capture HIV and inhibit HIV infectivity in the eye. So we would like to analyze the relationship between HIV load and NETs expression in the intraocular fluid, observe the behavior of NETs capturing HIV particles in retinal tissue, to confirm the role of NETs on HIV in the eye. Meanwhile, by breaking the integrity of DNA structure, using specific protein inhibitors, to explore the mechanism of NETs inhibit HIV infecting microglia in vitro, may provide a theoretical basis for the clearance of HIV target cells.