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首页> 外文期刊>American Journal of Pathology: Official Publication of the American Association of Pathologists >Insulin-like growth factor 2 receptor is an IFNgamma-inducible microglial protein that facilitates intracellular HIV replication: implications for HIV-induced neurocognitive disorders.
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Insulin-like growth factor 2 receptor is an IFNgamma-inducible microglial protein that facilitates intracellular HIV replication: implications for HIV-induced neurocognitive disorders.

机译：胰岛素样生长因子2受体是一种IFngamma诱导的小胶质蛋白，便于细胞内HIV复制：对HIV诱导的神经认知障碍的影响。

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摘要

Insulin-like growth factor 2 receptor (IGF2R), also known as cation-independent mannose 6-phosphate (M6P) receptor, is a transmembrane glycoprotein localized in the trans-Golgi region and is involved in targeting both M6P-bearing enzymes and IGF2 to the lysosomal compartment. During development, IGF2R plays a crucial role in removing excess growth factors from both tissue and blood. Due to the perinatal lethality of the global Igf2r knockout, the function of IGF2R in adults, particularly in the CNS, is not known. We made a novel observation that IGF2R is highly expressed in microglial nodules in human brains with HIV encephalitis. In vitro, microglial IGF2R expression was uniquely enhanced by IFNgamma among the several cytokines and TLR ligands examined. Furthermore, in several in vitro models of HIV infection, including human and murine microglia, macrophages, and nonmacrophage cells, IGF2R is repeatedly shown to be a positive regulator of HIV infection. IGF2R RNAi also down-regulated the production of the IP-10 chemokine in HIV-infected human microglia. Injection of VSVg env HIV into mouse brain induced HIV p24 expression in neurons, the only cell type normally expressing IGF2R in the adult brain. Our results demonstrate a novel role for IGF2R as an inducible microglial protein involved in regulation of HIV and chemokine expression. Mice with the Csf1r- driven Igf2r knockout should be useful for the investigation of macrophage-specific IGF2R function.
机译：胰岛素样生长因子2受体（IGF2R），也称为阳离子甘露糖6-磷酸（M6P）受体，是在反式 - 高尔基地区局部局部局部化的跨膜糖蛋白，并参与靶向M6P轴承酶和IGF2至溶酶体隔室。在开发过程中，IGF2R在去除组织和血液中的过度生长因子方面发挥至关重要的作用。由于全球IGF2R淘汰的围产期杀伤性，IGF2R在成人中的功能，特别是在CNS中的功能尚不清楚。我们做出了一种新颖的观察，即IGF2R在具有HIV脑炎的人体大脑中的小胶质状结节中高度表达。在体外，通过IFnymama在检查的几种细胞因子和TLR配体中，微胶质IGF2R表达唯一地增强。此外，在艾滋病毒感染的几种体外模型中，包括人和鼠髓小胶质细胞，巨噬细胞和非引发细胞，反复显示IGF2R是艾滋病毒感染的阳性调节剂。 IGF2R RNAI还将下调艾滋病毒感染人微胶质细胞的IP-10趋化因子的生产。将VSVG Even HIV注射到神经元中的小鼠脑诱导的HIV P24表达中，唯一唯一在成年脑中表达IGF2R的细胞型。我们的结果表明了IGF2R作为参与艾滋病毒和趋化因子表达的调节的诱导微胶质蛋白的新颖作用。具有CSF1R-驱动的IGF2R敲除的小鼠应该有助于调查巨噬细胞特异性IGF2R功能。

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