IMMUNOPHENOTYPIC DIVERSITY OF BRAIN MACROPHAGES: IMPLICATIONS FOR NEUROAIDS

脑巨噬细胞的免疫表型多样性：对神经艾滋病的影响

• 批准号: 7349054
• 负责人: JUAN BORDA
• 金额: $ 6.54万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7349054
• 关键词: IMMUNOPHENOTYPIC; DIVERSITY; BRAIN; MACROPHAGES; IMPLICATIONS

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. Infection of humans with HIV or macaques with SIV often leads to an encephalitis (HIVE or SIVE) characterized by perivascular accumulations of macrophages and multinucleated giant cells, many of which are productively infected. It is assumed that the development of SIVE/HIVE is associated with increased migration (and retention) of circulating monocytes into the brain. The immigration of these monocytes into the brain would facilitate neuroinvasion and provide additional cells for infection. Direct assessment of this hypyothesis has been frustrated by the lack of specific markers that can easily differentiate among perivascular macrophages, recently immigrated monocytes, and parenchymal microglia. Recently, expression of CD14 and CD45 in conjunction with CD11b has been used to differentiate parenchymal microglia (CD11b+ CD14¿CD45¿) from perivascular macrophages (CD11b+ CD14+CD45+) and define the latter as the primary cell type productively infected in the CNS. It was clear, however, that the population of SIV-infected cells that shared expression of CD11b, CD14 and CD45 was heterogeneous. This suggested that we might be looking at several populations of cells including those that had recently immigrated from the blood. To assess this further and try to define the immunophenotypes of additional populations of brain macrophages, including those that had recently entered the CNS, we performed multilabel confocal microscopy for a variety of cell markers combined with in situ hybridzation (ISH) for SIV. The markers used included CD11b, CD14, CD45, myeloid histocyte antigen (clone MAC387), myeloid related proteins 8 (MRP8) and 14 (MRP14), CD68, HAM56, LN5 and CD163. The presence of MAC387+, MRP8+, MRP14+ cells not infected by SIV could represent either recently recruited monocyte/macrophages or a population of macrophages resistant to infection. Lastly, CD163 appears to label ¿activated¿ microglia as no labeling of parenchymal cells was seen in normal animals, while in animals with encephalitis there labeling was extensive.

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。人类感染HIV或猕猴感染SIV通常导致脑炎（HIVE或SIVE），其特征为巨噬细胞和多核巨细胞的血管周围积聚，其中许多是生产性感染。假设SIVE/HIVE的发展与循环单核细胞向脑中的迁移（和保留）增加有关。这些单核细胞向脑内的迁移将促进神经侵袭，并为感染提供额外的细胞。由于缺乏特异性标志物，无法很容易区分血管周围巨噬细胞、最近迁移的单核细胞和实质小胶质细胞，因此无法直接评估这种假说。最近，CD 14和CD 45与CD 11b的表达已被用于区分实质小胶质细胞（CD 11b + CD 14 <$CD 45 <$）和血管周围巨噬细胞（CD 11b + CD 14 + CD 45+），并将后者定义为CNS中有效感染的主要细胞类型。然而，很明显，SIV感染的细胞群体共享CD 11b，CD 14和CD 45的表达是异质的。这表明我们可能正在研究几个细胞群，包括那些最近从血液中迁移的细胞。为了进一步评估这一点，并试图确定其他人群的脑巨噬细胞，包括那些最近进入中枢神经系统的免疫表型，我们进行了多标记共聚焦显微镜的各种细胞标志物结合原位杂交（ISH）的SIV。使用的标志物包括CD 11b、CD 14、CD 45、髓样组织细胞抗原（克隆MAC 387）、髓样相关蛋白8（MRP 8）和14（MRP 14）、CD 68、HAM 56、LN 5和CD 163。未被SIV感染的MAC 387+、MRP 8+、MRP 14+细胞的存在可能代表最近募集的单核细胞/巨噬细胞或对感染具有抗性的巨噬细胞群体。最后，CD 163似乎标记了活化的小胶质细胞，因为在正常动物中没有看到实质细胞的标记，而在脑炎动物中，标记是广泛的。