{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:14:55Z","timestamp":1790810095290,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011710","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,1,24]],"date-time":"2024-01-24T00:00:00Z","timestamp":1706054400000}}],"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T00:00:00Z","timestamp":1704931200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI120846"],"award-info":[{"award-number":["R01AI120846"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21AI155122"],"award-info":[{"award-number":["R21AI155122"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["F31NS118865"],"award-info":[{"award-number":["F31NS118865"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p><jats:italic>Toxoplasma gondii<\/jats:italic> is an obligate intracellular parasite that infects one-third of the world\u2019s human population and establishes infection in the brain. Cerebral immune cell infiltration is critical for controlling the parasite, but little is known about the molecular cues guiding immune cells to the brain during infection. Activated astrocytes produce CCL2, a chemokine that mediates inflammatory monocyte recruitment to tissues by binding to the CCR2 receptor. We detected elevated CCL2 production in the brains of C57BL\/6J mice by 15 days after <jats:italic>T<\/jats:italic>. <jats:italic>gondii<\/jats:italic> infection. Utilizing confocal microscopy and intracellular flow cytometry, we identified microglia and brain-infiltrating myeloid cells as the main producers of CCL2 during acute infection, and CCL2 was specifically produced in regions of parasite infection in the brain. In contrast, astrocytes became the dominant CCL2 producer during chronic <jats:italic>T<\/jats:italic>. <jats:italic>gondii<\/jats:italic> infection. To determine the role of astrocyte-derived CCL2 in mobilizing immune cells to the brain and controlling <jats:italic>T<\/jats:italic>. <jats:italic>gondii<\/jats:italic> infection, we generated GFAP-Cre x CCL2<jats:sup>fl\/fl<\/jats:sup> mice, in which astrocytes are deficient in CCL2 production. We observed significantly decreased immune cell recruitment and increased parasite burden in the brain during chronic, but not acute, infection of mice deficient in astrocyte CCL2 production, without an effect on peripheral immune responses. To investigate potential mechanisms explaining the reduced control of <jats:italic>T<\/jats:italic>. <jats:italic>gondii<\/jats:italic> infection, we analyzed key antimicrobial and immune players in host defense against <jats:italic>T<\/jats:italic>. <jats:italic>gondii<\/jats:italic> and detected a reduction in iNOS<jats:sup>+<\/jats:sup> myeloid cells, and <jats:italic>T<\/jats:italic>. <jats:italic>gondii<\/jats:italic>-specific CD4<jats:sup>+<\/jats:sup> T cells in the knockout mice. These data uncover a critical role for astrocyte-derived CCL2 in immune cell recruitment and parasite control in the brain during chronic, but not acute, <jats:italic>T<\/jats:italic>. <jats:italic>gondii<\/jats:italic> infection.<\/jats:p>","DOI":"10.1371\/journal.ppat.1011710","type":"journal-article","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T18:40:52Z","timestamp":1704998452000},"page":"e1011710","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":20,"title":["Deficiency in astrocyte CCL2 production reduces neuroimmune control of Toxoplasma gondii infection"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2491-1074","authenticated-orcid":true,"given":"Stephanie B.","family":"Orchanian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Still","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tajie H.","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3366-6840","authenticated-orcid":true,"given":"Melissa B.","family":"Lodoen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,1,11]]},"reference":[{"key":"ppat.1011710.ref001","doi-asserted-by":"crossref","first-page":"16001","DOI":"10.1038\/nmicrobiol.2016.1","article-title":"Endothelial cells are a replicative niche for entry of Toxoplasma gondii to the central nervous system","volume":"1","author":"C Konradt","year":"2016","journal-title":"Nat Microbiol"},{"issue":"4","key":"ppat.1011710.ref002","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.chom.2019.09.008","article-title":"In Vivo CRISPR Screen Identifies Tg WIP as a Toxoplasma Modulator of Dendritic Cell Migration","volume":"26","author":"LO Sangar\u00e9","year":"2019","journal-title":"Cell Host Microbe"},{"issue":"1","key":"ppat.1011710.ref003","first-page":"112","article-title":"Toxoplasmosis of Animals and Humans","volume":"3","author":"JP Webster","year":"2010","journal-title":"Parasit Vectors"},{"issue":"12","key":"ppat.1011710.ref004","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1016\/j.ijpara.2009.04.003","article-title":"Toxoplasmosis snapshots: Global status of Toxoplasma gondii seroprevalence and implications for pregnancy and congenital toxoplasmosis","volume":"39","author":"G Pappas","year":"2009","journal-title":"Int J Parasitol"},{"issue":"4987","key":"ppat.1011710.ref005","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1038\/206961a0","article-title":"Experimental Transmission of Toxoplasma gondii","volume":"206","author":"WM Hutchinson","year":"1965","journal-title":"Nature"},{"issue":"9","key":"ppat.1011710.ref006","first-page":"952","article-title":"Epidemiological study on toxoplasmosis: the influence of cooking slaughter-animal meat on the incidence of human infection","volume":"10","author":"G Desmonts","year":"1965","journal-title":"Rev Fr Etud Clin Biol"},{"issue":"20","key":"ppat.1011710.ref007","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1056\/NEJM197405162902003","article-title":"Congenital toxoplasmosis. 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