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The ChP\u2013CSF 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\u2010associated encephalophagy. Here, we used human ChP organoid (ChPO) to model herpes simplex virus type 1 (HSV\u20101) infection and found ChP epithelial cells were highly susceptible to HSV\u20101. Since the current ChPO model lacks a functional innate immune component, particularly microglia, we next developed a new microglia\u2010containing ChPO\u00a0model, and found microglia could effectively limit HSV\u20101 infection and protect epithelial barrier in ChPOs. Furthermore, we found the innate immune cyclic GMP\u2010AMP synthase\u00a0(cGAS)\u2013STING pathway and its downstream interferon response were essential, as cGAS inhibitor RU.512 or STING inhibitor H\u2010151 abolished microglia antiviral function and worsened ChP barrier in organoids. These results together indicated that cGAS\u2013STING pathway coordinates antiviral response in ChP and contributes to treating sepsis or related neurological conditions.<\/jats:p>","DOI":"10.1002\/jmv.28472","type":"journal-article","created":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T11:54:14Z","timestamp":1673006054000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Microglia innate immune response contributes to the antiviral defense and blood\u2013CSF barrier function in human choroid plexus organoids during HSV\u20101 infection"],"prefix":"10.1002","volume":"95","author":[{"given":"Haowen","family":"Qiao","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, Keck School of Medicine, Center for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute University of Southern California Los Angeles California 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