MICROGLIA AND SIV NEUROPATHOGENESIS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项研究的重点是血管周围巨噬细胞作为SIV在中枢神经系统(CNS)产生感染的靶细胞。越来越多的证据强调了中枢神经系统巨噬细胞的作用，其中一些细胞感染了艾滋病毒，导致了神经系统疾病。我们认为，在艾滋病和SIV脑炎(SIVE)动物中，中枢神经系统血管周围巨噬细胞是早期和晚期感染的主要细胞。我们以前利用髓系细胞表达的免疫标记物的组合，建立了血管周围巨噬细胞和实质小胶质细胞之间的表型差异，并确定血管周围巨噬细胞是生产性SIV感染的主要目标。指导这一建议的工作假设是，骨髓单核/巨噬细胞是潜在的中枢神经系统血管周围巨噬细胞，可以在SIV感染的猕猴中识别出来，并在它们运输到中枢神经系统时进行研究。我们假设免疫系统控制着骨髓中血管周围巨噬细胞前体细胞的SIV感染水平；它们通过血液的激活交通，并在中枢神经系统中积累。最后，我们假设SIV感染的血管周围巨噬细胞在艾滋病发生后的运输和聚集，而不是SIV感染后早期进入中枢神经系统的SIV，与神经元损伤和损伤相关。

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.