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- W4313646065 abstract "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." @default.
- W4313646065 created "2023-01-07" @default.
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- W4313646065 date "2023-01-16" @default.
- W4313646065 modified "2023-10-14" @default.
- W4313646065 title "Microglia innate immune response contributes to the antiviral defense and blood–CSF barrier function in human choroid plexus organoids during HSV‐1 infection" @default.
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- W4313646065 doi "https://doi.org/10.1002/jmv.28472" @default.
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