AUTHOR=Scheunemann Johanna F. , Reichwald Julia J. , Korir Patricia Jebett , Kuehlwein Janina M. , Jenster Lea-Marie , Hammerschmidt-Kamper Christiane , Lewis Matthew D. , Klocke Katrin , Borsche Max , Schwendt Kim E. , Soun Camille , Thiebes Stephanie , Limmer Andreas , Engel Daniel R. , Mueller Ann-Kristin , Hoerauf Achim , Hübner Marc P. , Schumak Beatrix TITLE=Eosinophils Suppress the Migration of T Cells Into the Brain of Plasmodium berghei-Infected Ifnar1-/- Mice and Protect Them From Experimental Cerebral Malaria JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.711876 DOI=10.3389/fimmu.2021.711876 ISSN=1664-3224 ABSTRACT=

Cerebral malaria is a potentially lethal disease, which is caused by excessive inflammatory responses to Plasmodium parasites. Here we use a newly developed transgenic Plasmodium berghei ANKA (PbA_Ama1OVA) parasite that can be used to study parasite-specific T cell responses. Our present study demonstrates that Ifnar1^-/- mice, which lack type I interferon receptor-dependent signaling, are protected from experimental cerebral malaria (ECM) when infected with this novel parasite. Although CD8⁺ 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 Ifnar1^-/- mice and wild type mice suffering from ECM. Importantly, CD8⁺ T cells were increased in the spleens of ECM-protected Ifnar1^-/- 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⁺ T cell infiltration into the brain and increased ECM induction in PbA_Ama1OVA-infected Ifnar1^-/- mice. However, eosinophil-depletion did not reduce the CD8⁺ T cell population in the spleen or reduce splenic CCL5 concentrations. Our study demonstrates that eosinophils impact CD8⁺ T cell migration and proliferation during PbA_Ama1OVA-infection in Ifnar1^-/- mice and thereby are contributing to the protection from ECM.