{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:29:37Z","timestamp":1787005777132,"version":"build-2736575974"},"reference-count":50,"publisher":"National Academy of Sciences","issue":"11","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01 DK122790"],"award-info":[{"award-number":["R01 DK122790"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015691","name":"HHS | NIH | NIAID | Division of Microbiology and Infectious Diseases","doi-asserted-by":"publisher","award":["K08 AR084597"],"award-info":[{"award-number":["K08 AR084597"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["T32 DK077653"],"award-info":[{"award-number":["T32 DK077653"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,3,17]]},"abstract":"<jats:p>Functional gastrointestinal (GI) tract disorders affect a substantial proportion of the global population and are often preceded by intestinal infections that cause injury to enteric neurons and glia through unrestrained immune responses. However, the mechanisms that limit infection-induced inflammation and protect the enteric nervous system remain poorly understood. Here, we defined such neuron\u2013glia\u2013macrophage interactions after West Nile virus (WNV) infection; this model neurotropic virus causes GI tract dysmotility in mice via injury of enteric neurons through a T cell\u2013mediated cytolytic mechanism. In response to WNV infection, RNA sequencing analysis showed that resident muscularis macrophages upregulate antiviral, proinflammatory, and immunomodulatory genes. Whereas pharmacological depletion of resident macrophages did not affect the viral burden in the GI tract, it instead reshaped the enteric glial response to WNV, resulting in excessive production of T cell and neutrophil chemoattractants. The amplified recruitment of these immune cell types worsened enteric neuronal injury. Together, our findings identify resident muscularis macrophages as key regulators of glia-driven inflammation during enteric viral infection and reveal their role in protecting enteric neurons from immune-mediated damage.<\/jats:p>","DOI":"10.1073\/pnas.2537058123","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T17:47:37Z","timestamp":1773164857000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":2,"title":["Macrophage\u2013glia interactions regulate immune damage to enteric neurons during West Nile virus infection"],"prefix":"10.1073","volume":"123","author":[{"given":"Hana","family":"Janova","sequence":"first","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine","place":["Saint Louis"]},{"name":"Center for Neuroimmunology and Glial Biology, Institute of Molecular Medicine, University of Texas Health Science Center","place":["Houston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang R.","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine","place":["Saint Louis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Akgul","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine","place":["Saint Louis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meredith","family":"Schatz","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine","place":["Saint Louis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel M.","family":"Alligood","sequence":"additional","affiliation":[{"name":"Department of Surgery, Washington University School of Medicine","place":["Saint Louis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8748-0761","authenticated-orcid":false,"given":"David M.","family":"Alvarado","sequence":"additional","affiliation":[{"name":"Department of Surgery, Washington University School of Medicine","place":["Saint Louis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa B.","family":"Thackray","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine","place":["Saint Louis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6023-3901","authenticated-orcid":false,"given":"Thaddeus S.","family":"Stappenbeck","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Immunity, Cleveland Clinic","place":["Cleveland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8791-3165","authenticated-orcid":false,"given":"Michael S.","family":"Diamond","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine","place":["Saint Louis"]},{"name":"Department of Pathology and Immunology, Washington University School of Medicine","place":["Saint Louis"]},{"name":"Department of Molecular Microbiology, Washington University School of Medicine","place":["Saint Louis"]},{"name":"The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine","place":["Saint Louis"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i14.3976"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.04.014"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000010631"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.08.069"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI181421"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.12.002"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.05.008"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.08.005"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.12.023"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.04.050"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.78558"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.04.021"},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","unstructured":"M. M. Ahmadzai L. Seguella B. D. Gulbransen Circuit-specific enteric glia regulate intestinal motor neurocircuits. Proc. Natl. Acad. Sci. 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