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The eukaryotic parasite\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    colonizes the brain of its hosts, and initiates robust immune cell recruitment, but little is known about pattern recognition of\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    within brain tissue. The host damage signal IL-33 is one protein that has been implicated in control of chronic\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    infection, but, like many other pattern recognition pathways, IL-33 can signal peripherally, and the specific impact of IL-33 signaling within the brain is unclear. Here, we show that IL-33 is expressed by oligodendrocytes and astrocytes during\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    infection, is released locally into the cerebrospinal fluid of\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    -infected animals, and is required for control of infection. IL-33 signaling promotes chemokine expression within brain tissue and is required for the recruitment and\/or maintenance of blood-derived anti-parasitic immune cells, including proliferating, IFN-\u03b3-expressing T cells and iNOS-expressing monocytes. Importantly, we find that the beneficial effects of IL-33 during chronic infection are not a result of signaling on infiltrating immune cells, but rather on radio-resistant responders, and specifically, astrocytes. Mice with IL-33 receptor-deficient astrocytes fail to mount an adequate adaptive immune response in the CNS to control parasite burden\u2013demonstrating, genetically, that astrocytes can directly respond to IL-33\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Together, these results indicate a brain-specific mechanism by which IL-33 is released locally, and sensed locally, to engage the peripheral immune system in controlling a pathogen.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1009027","type":"journal-article","created":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T13:53:11Z","timestamp":1603806791000},"page":"e1009027","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":50,"title":["Astrocytes promote a protective immune response to brain Toxoplasma gondii infection via IL-33-ST2 signaling"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0260-2606","authenticated-orcid":true,"given":"Katherine M.","family":"Still","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8200-7550","authenticated-orcid":true,"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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5347-7502","authenticated-orcid":true,"given":"Oyebola O.","family":"Oyesola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4757-8315","authenticated-orcid":true,"given":"Simon P.","family":"Fr\u00fch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1903-7570","authenticated-orcid":true,"given":"Lauren M.","family":"Webb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Smirnov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4298-9609","authenticated-orcid":true,"given":"Michael A.","family":"Kovacs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6842-8175","authenticated-orcid":true,"given":"Maureen N.","family":"Cowan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1885-1850","authenticated-orcid":true,"given":"Nikolas W.","family":"Hayes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9937-1888","authenticated-orcid":true,"given":"Jeremy A.","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2822-296X","authenticated-orcid":true,"given":"Elia D.","family":"Tait Wojno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1355-2109","authenticated-orcid":true,"given":"Tajie H.","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,10,27]]},"reference":[{"issue":"5","key":"ppat.1009027.ref001","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1172\/JCI41911","article-title":"Trafficking of immune cells in the central nervous system","volume":"120","author":"EH Wilson","year":"2010","journal-title":"J Clin Invest"},{"issue":"11","key":"ppat.1009027.ref002","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1038\/nrmicro2858","article-title":"Modulation of innate immunity by Toxoplasma gondii virulence effectors","volume":"10","author":"CA Hunter","year":"2012","journal-title":"Nat Rev Microbiol"},{"issue":"3","key":"ppat.1009027.ref003","doi-asserted-by":"crossref","first-page":"e90203","DOI":"10.1371\/journal.pone.0090203","article-title":"Toxoplasmosis\u2014a global threat. 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