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When astrocytes become reactive, maintenance of the inflammatory state and its functional implications throughout chronic neuroinflammation are all poorly understood. Several models of acute inflammation have revealed astrocyte subpopulations that go beyond a two\u2010activation state model, instead encompassing distinct functional subsets. However, how reactive astrocyte (RA) subsets evolve over time during chronic inflammatory disease or infection has been difficult to address. Here we use a prolific human pathogen, <jats:italic>Toxoplasma gondii<\/jats:italic>, that causes lifelong infection in the brain alongside a <jats:italic>Lcn2CreERT2<\/jats:italic> reporter mouse line to examine reactive astrocyte subsets during chronic neuroinflammation. Single\u2010cell RNA sequencing revealed diverse astrocyte populations including transcriptionally unique <jats:italic>Lcn2CreERT2<\/jats:italic>+ RAs which change over the course of infection in a subset\u2010dependent manner. In addition to an immune\u2010regulating <jats:italic>Lcn2CreERT2<\/jats:italic>+ astrocyte population enriched with gene transcripts encoding chemokines CCL5, CXCL9, CXCL10, and receptors CCR7 and IL7R, a specific subset of <jats:italic>Lcn2CreERT2<\/jats:italic>+ astrocytes highly expressed <jats:italic>transthyretin<\/jats:italic> (<jats:italic>Ttr<\/jats:italic>), a secreted carrier protein involved in glycolytic enzyme activation and potential vasculature regulation and angiogenesis. These findings provide novel information about the evolution and diversity of reactive astrocyte subtypes and functional signatures at different stages of infection, revealing an undocumented role for transthyretin\u2010expressing astrocytes in immune regulation at the central nervous system (CNS) vasculature.<\/jats:p>","DOI":"10.1002\/glia.70053","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T04:29:16Z","timestamp":1752121756000},"page":"2003-2024","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Diverse Subpopulations of Reactive Astrocytes Following Chronic Toxoplasma Infection"],"prefix":"10.1002","volume":"73","author":[{"given":"Zoe A.","family":"Figueroa","sequence":"first","affiliation":[{"name":"Division of Biomedical Sciences, School of Medicine University of California  Riverside California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose 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