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Immunol."],"abstract":"<jats:p>Cerebral malaria is a potentially lethal disease, which is caused by excessive inflammatory responses to<jats:italic>Plasmodium<\/jats:italic>parasites. Here we use a newly developed transgenic<jats:italic>Plasmodium berghei<\/jats:italic>ANKA (<jats:italic>PbA<jats:sub>Ama1<\/jats:sub>OVA<\/jats:italic>) parasite that can be used to study parasite-specific T cell responses. Our present study demonstrates that<jats:italic>Ifnar1<jats:sup>-\/-<\/jats:sup><\/jats:italic>mice, which lack type I interferon receptor-dependent signaling, are protected from experimental cerebral malaria (ECM) when infected with this novel parasite. Although CD8<jats:sup>+<\/jats:sup>T cell responses generated in the spleen are essential for the development of ECM, we measured comparable parasite-specific cytotoxic T cell responses in ECM-protected<jats:italic>Ifnar1<jats:sup>-\/-<\/jats:sup><\/jats:italic>mice and wild type mice suffering from ECM. Importantly, CD8<jats:sup>+<\/jats:sup>T cells were increased in the spleens of ECM-protected<jats:italic>Ifnar1<jats:sup>-\/-<\/jats:sup><\/jats:italic>mice and the blood-brain-barrier remained intact. This was associated with elevated splenic levels of CCL5, a T cell and eosinophil chemotactic chemokine, which was mainly produced by eosinophils, and an increase in eosinophil numbers. Depletion of eosinophils enhanced CD8<jats:sup>+<\/jats:sup>T cell infiltration into the brain and increased ECM induction in<jats:italic>PbA<jats:sub>Ama1<\/jats:sub>OVA<\/jats:italic>-infected<jats:italic>Ifnar1<jats:sup>-\/-<\/jats:sup><\/jats:italic>mice. However, eosinophil-depletion did not reduce the CD8<jats:sup>+<\/jats:sup>T cell population in the spleen or reduce splenic CCL5 concentrations. Our study demonstrates that eosinophils impact CD8<jats:sup>+<\/jats:sup>T cell migration and proliferation during<jats:italic>PbA<jats:sub>Ama1<\/jats:sub>OVA<\/jats:italic>-infection in<jats:italic>Ifnar1<jats:sup>-\/-<\/jats:sup><\/jats:italic>mice and thereby are contributing to the protection from ECM.<\/jats:p>","DOI":"10.3389\/fimmu.2021.711876","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T08:24:46Z","timestamp":1632990286000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Eosinophils Suppress the Migration of T Cells Into the Brain of Plasmodium berghei-Infected Ifnar1-\/- Mice and Protect Them From Experimental Cerebral Malaria"],"prefix":"10.3389","volume":"12","author":[{"given":"Johanna F.","family":"Scheunemann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia J.","family":"Reichwald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia Jebett","family":"Korir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janina M.","family":"Kuehlwein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea-Marie","family":"Jenster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Hammerschmidt-Kamper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D.","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Klocke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Borsche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim E.","family":"Schwendt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Soun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Thiebes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Limmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel R.","family":"Engel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann-Kristin","family":"Mueller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim","family":"Hoerauf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc P.","family":"H\u00fcbner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrix","family":"Schumak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,30]]},"reference":[{"key":"B1","volume-title":"World Malaria Report 2019. 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