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Microglia innate immune response contributes to the antiviral defense and blood-CSF barrier function in human choroid plexus organoids during HSV-1 infection
Qiao, HW; Chiu, YP; Liang, XY; Xia, SZ; Ayrapetyan, M; Liu, SQ; He, CL; Song, RC; Zeng, JX; Deng, XX; Yuan, WM; Zhao, Z
2023
发表期刊JOURNAL OF MEDICAL VIROLOGY
ISSN0146-6615
卷号95期号:2
摘要The choroid plexus (ChP) is the source of cerebrospinal fluid (CSF). The ChP-CSF system not only provides the necessary cushion for the brain but also works as a sink for waste clearance. During sepsis, pathogens and host immune cells can weaken the ChP barrier and enter the brain, causing cerebral dysfunctions known as sepsis-associated encephalophagy. Here, we used human ChP organoid (ChPO) to model herpes simplex virus type 1 (HSV-1) infection and found ChP epithelial cells were highly susceptible to HSV-1. Since the current ChPO model lacks a functional innate immune component, particularly microglia, we next developed a new microglia-containing ChPO model, and found microglia could effectively limit HSV-1 infection and protect epithelial barrier in ChPOs. Furthermore, we found the innate immune cyclic GMP-AMP synthase (cGAS)-STING pathway and its downstream interferon response were essential, as cGAS inhibitor RU.512 or STING inhibitor H-151 abolished microglia antiviral function and worsened ChP barrier in organoids. These results together indicated that cGAS-STING pathway coordinates antiviral response in ChP and contributes to treating sepsis or related neurological conditions.
收录类别SCI
语种英语
文献类型期刊论文
条目标识符http://ir.kiz.ac.cn/handle/152453/14389
专题昆明动物研究所
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GB/T 7714
Qiao, HW,Chiu, YP,Liang, XY,et al. Microglia innate immune response contributes to the antiviral defense and blood-CSF barrier function in human choroid plexus organoids during HSV-1 infection[J]. JOURNAL OF MEDICAL VIROLOGY,2023,95(2).
APA Qiao, HW.,Chiu, YP.,Liang, XY.,Xia, SZ.,Ayrapetyan, M.,...&Zhao, Z.(2023).Microglia innate immune response contributes to the antiviral defense and blood-CSF barrier function in human choroid plexus organoids during HSV-1 infection.JOURNAL OF MEDICAL VIROLOGY,95(2).
MLA Qiao, HW,et al."Microglia innate immune response contributes to the antiviral defense and blood-CSF barrier function in human choroid plexus organoids during HSV-1 infection".JOURNAL OF MEDICAL VIROLOGY 95.2(2023).
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