MICROGLIA AND SIV NEUROPATHOGENESIS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。本研究的重点是在血管周围的巨噬细胞作为生产性SIV感染的中枢神经系统（CNS）的目标。越来越多的证据强调了CNS巨噬细胞的作用，其中一些是HIV感染的，有助于神经系统疾病。我们提出，CNS血管周围巨噬细胞是一个主要的细胞，在艾滋病和SIV脑炎（SIVE）的动物感染早期和终末。我们以前已经建立了，使用组合的免疫标记物表达的细胞的骨髓谱系，表型之间的差异血管周围巨噬细胞和实质小胶质细胞，并确定血管周围巨噬细胞作为生产性SIV感染的主要目标。 指导该建议的工作假设是，骨髓单核细胞/巨噬细胞是潜在的CNS血管周围巨噬细胞，可以在SIV感染的猕猴中鉴定，并在它们运输到CNS时进行研究。我们假设免疫系统控制SIV感染骨髓中血管周围巨噬细胞前体的水平;它们通过血液的活化交通，以及在CNS中的积累。最后，我们假设，交通和积累的SIV感染血管周围的巨噬细胞，艾滋病的发展后，而不是SIV感染后早期进入中枢神经系统，与神经元损伤和损伤。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The focus of this study is on the perivascular macrophage as target of productive SIV infection in the central nervous system (CNS). Increasing evidence underscores the role of CNS macrophages, some of which are HIV infected, contributing to neurologic disease. We propose that CNS perivascular macrophages are a primary cell productively infected early and terminally, in animals with AIDS and SIV encephalitis (SIVE). We have established previously, using combinations of immune markers expressed by cells of the myeloid lineage, phenotypic differences between perivascular macrophages and parenchymal microglia and identified perivascular macrophages as a primary target of productive SIV infection. The working hypothesis that guides this proposal is that bone marrow monocyte/macrophages that are potential CNS perivascular macrophages, can be identified in SIV infected macaques and studied as they traffic to the CNS. We hypothesize that the immune system controls the level of SIV infection of perivascular macrophage precursors in the bone marrow; their activation traffic through the blood, and accumulation in the CNS. Lastly, we hypothesize that the traffic and accumulation of SIV infected perivascular macrophages, after the development of AIDS, and not SIV that enters the CNS early after infection, correlate with neuronal damage and injury.