神经元损伤/缺失是造成HIV相关性痴呆(HAD)的根本原因，其确切机制尚未阐明。最新研究表明，慢性HIV感染患者外周血中的髓系抑制性细胞(MDSC)数量显著增多。在预实验中，我们发现：HIV/Tat能明显促进MDSC细胞表面趋化因子受体CCR2、CXCR4的表达，增加NO、iNOS和Arg1的产生；受到趋化因子CCL2作用后，通过血脑屏障模型的MDSC数量显著增多。本课题拟以HIV感染、活化、募集MDSC形成正反馈为切入点，重点研究HIV/Tat活化的MDSC对神经元生存/凋亡、细胞自噬、能量代谢、细胞骨架重排及对谷氨酸敏感性的影响，并初步探明MDSC对巨噬细胞/小胶质细胞、星形胶质细胞损伤神经元是否具有协同效应。本研究在细胞及分子水平上深入探讨MDSC能否作为脑内新型HIV感染细胞，在HAD神经元损伤中发挥重要作用，不仅有助于进一步阐明HAD的发病机理，也为该疾病的防治提供新的药物靶标。

Neurons impairment or deficiency is the key cause for HIV-associated dementia (HAD), but the exact mechanism has not been elucidated. The latest studies have found that the number of myeloid derived suppressor cells (MDSC) in the peripheral blood of patients with chronic HIV-1 infection increased significantly.Our preliminary experiments results shown that HIV Tat significantly enhanced the expression of CCR2 and CXCR4 on MDSC and the production of NO,iNOS and Arg1. The number of MDSC that pass through blood-brain barrier (BBB) model after chemoattractanted through the chemokine CCL2 was also increased significantly.This project is intended to using HIV-infection, activation and recruit to form a positive feedback loop as the starting point, focus on the effect of HIV/Tat activated MDSC on the autophagy and apoptosis, energy metabolism, cytoskeletal rearrangement and glutamate sensitivity of neurons,and initially proved wheather MDSC have a synergistic effect in macrophages/microglia and astrocytes in neuronal impairment.Our project will to explore the effects and mechanisms of MDSC act as a new HIV infected cell type on neuronal impairment which is involved in HAD pathogenesis in the cellular and molceular level. It will not only help us to further elucidate the pathogenesis of HAD, and also provide new drug targets for the effective prevention and treatment of the disease.