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Constant immune pressure, notably IFN-\u03b3-STAT1 signaling, is required for preventing fatal pathology during\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    infection. Here, we report that abrogation of STAT1 signaling in microglia, the resident immune cells of the CNS, is sufficient to induce a loss of parasite control in the CNS and susceptibility to toxoplasmic encephalitis during the early stages of chronic infection. Using a microglia-specific genetic labeling and targeting system that discriminates microglia from blood-derived myeloid cells that infiltrate the brain during infection, we find that, contrary to previous\n                    <jats:italic>in vitro<\/jats:italic>\n                    reports, microglia do not express inducible nitric-oxide synthase (iNOS) during\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    infection\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Instead, transcriptomic analyses of microglia reveal that STAT1 regulates both (i) a transcriptional shift from homeostatic to \u201cdisease-associated microglia\u201d (DAM) phenotype conserved across several neuroinflammatory models, including\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    infection, and (ii) the expression of anti-parasitic cytosolic molecules that are required for eliminating\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    in a cell-intrinsic manner. Further, genetic deletion of\n                    <jats:italic>Stat1<\/jats:italic>\n                    from microglia during\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    challenge leads to fatal pathology despite largely equivalent or enhanced immune effector functions displayed by brain-infiltrating immune populations. Finally, we show that microglial STAT1-deficiency results in the overrepresentation of the highly replicative, lytic tachyzoite form of\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    , relative to its quiescent, semi-dormant bradyzoite form typical of chronic CNS infection. Our data suggest an overall protective role of CNS-resident microglia against\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    infection, illuminating (i) general mechanisms of CNS-specific immunity to infection (ii) and a clear role for IFN-STAT1 signaling in regulating a microglial activation phenotype observed across diverse neuroinflammatory disease states.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1010637","type":"journal-article","created":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T13:46:53Z","timestamp":1662472013000},"page":"e1010637","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":26,"title":["Microglial STAT1-sufficiency is required for resistance to toxoplasmic encephalitis"],"prefix":"10.1371","volume":"18","author":[{"given":"Maureen N.","family":"Cowan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Kovacs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ish","family":"Sethi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac W.","family":"Babcock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Still","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha J.","family":"Batista","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carleigh A.","family":"O\u2019Brien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy 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