IMPORTANCE OF MONOCYTES/MACROPHAGES IN AIDS

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。 人们普遍认为，在感染HIV-1的人类和感染SIV的猕猴中，CD4(+)T细胞的破坏和病毒载量是免疫缺陷的主要标志。然而，单核/巨噬细胞也是HIV/SIV感染的重要靶点，也是天然免疫和获得性免疫之间的关键纽带。因此，我们在恒河猴模型中研究了单核/巨噬细胞系细胞的变化是否与艾滋病的发病有关。在这里，我们表明，与组织巨噬细胞死亡相关的外周血单核细胞的大量周转与猕猴的艾滋病进展相关。更重要的是，单核细胞周转水平与CD4(+)T细胞计数无关，与病毒载量或淋巴细胞激活相比，它是预测艾滋病进展的更好的标志。我们的研究结果表明单核/巨噬细胞在艾滋病发病机制中的重要性，并提示单核/巨噬细胞的动态变化是艾滋病进展的一个新的标志物。

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. It is widely accepted that destruction of CD4(+) T cells and viral load are the primary markers for immunodeficiency in HIV-1-infected humans and in simian immunodeficiency virus (SIV)-infected macaques. However, monocyte/macrophages are also important targets of HIV/SIV infection and a critical link between innate and adaptive immunity. We therefore examined whether changes in cells of the monocyte/macrophage lineage could be linked to the pathogenesis of AIDS in the rhesus macaque model. Here, we show that massive turnover of peripheral monocytes associated with death of tissue macrophages correlates with AIDS progression in macaques. More importantly, the level of monocyte turnover was not linked to the CD4(+) T-cell count and was a better predictive marker for AIDS progression than was viral load or lymphocyte activation. Our results show the importance of monocyte/macrophages in the pathogenesis of AIDS and suggest the dynamic changes of the monocyte/macrophages as a new marker for AIDS progression.