Exosomes contribute to the transmission of anti-HIV activity from TLR3-activated brain microvascular endothelial cells to macrophages.
Exosomes contribute to the transmission of anti-HIV activity from TLR3-activated brain microvascular endothelial cells to macrophages.
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外泌体有助于将 TLR3 激活的脑微血管内皮细胞的抗 HIV 活性传递给巨噬细胞。
DOI：
10.1016/j.antiviral.2016.07.013
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发表时间：
2016-10
影响因子：
7.6
通讯作者：
Li JL
中科院分区：
文献类型：
--
作者：
Sun L;Wang X;Zhou Y;Zhou RH;Ho WZ;Li JL
人脑微血管内皮细胞（HBMECs）是血脑屏障（BBB）的主要细胞类型，在维持脑内环境稳定中起着关键作用。然而，它们在BBB先天免疫中对HIV侵入中枢神经系统（CNS）的作用仍有待确定。我们的早期工作表明，HBMEC的TLR 3信号可以产生抑制HIV在巨噬细胞中复制的抗病毒因子。本研究检查了来自TLR 3激活的HBMEC的外泌体是否介导抗病毒因子向巨噬细胞的细胞间转移。原代人巨噬细胞可以从TLR 3激活的HBMEC中摄取外来体。HBMEC衍生的外泌体含有多种抗病毒因子，包括mRNA和蛋白质水平的几个关键IFN刺激基因（ISG; ISG 15，ISG 56和Mx2）。从TLR 3激活的HBMEC培养上清液中消耗外泌体降低了巨噬细胞中HBMEC介导的抗HIV活性。总之，我们证明了HBMEC脱落的外泌体能够将抗病毒分子转运到巨噬细胞。这一发现表明，HIV非允许性BBB细胞（HBMEC）可能有助于恢复HIV感染的巨噬细胞中的抗病毒状态，这可能是对抗HIV神经侵袭的防御机制。
Human brain microvascular endothelial cells (HBMECs), the major cell type in the blood-brain barrier (BBB), play a key role in maintaining brain homeostasis. However, their role in the BBB innate immunity against HIV invasion of the central nervous system (CNS) remains to be determined. Our early work showed that TLR3 signaling of HBMECs could produce the antiviral factors that inhibit HIV replication in macrophages. The present study examined whether exosomes from TLR3-activated HBMECs mediate the intercellular transfer of antiviral factors to macrophages. Primary human macrophages could take up exosomes from TLR3-activated HBMECs. HBMECs-derived exosomes contained multiple antiviral factors, including several key IFN-stimulated genes (ISGs; ISG15, ISG56, and Mx2) at mRNA and protein levels. The depletion of exosomes from TLR3-activated HBMECs culture supernatant diminished HBMECs-mediated anti-HIV activity in macrophages. In conclusion, we demonstrate that exosomes shed by HBMECs are able to transport the antiviral molecules to macrophages. This finding suggests the possibility that HIV nonpermissive BBB cells (HBMECs) can help to restore the antiviral state in HIV-infected macrophages, which may be a defense mechanism against HIV neuroinvasion.