Eosinophils Suppress the Migration of T Cells Into the Brain of Plasmodium berghei -Infected Ifnar1 -/- Mice and Protect Them From Experimental Cerebral Malaria.

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 _Ama1 OVA ) 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 _Ama1 OVA -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 _Ama1 OVA -infection in Ifnar1 ^-/- mice and thereby are contributing to the protection from ECM.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Scheunemann, Reichwald, Korir, Kuehlwein, Jenster, Hammerschmidt-Kamper, Lewis, Klocke, Borsche, Schwendt, Soun, Thiebes, Limmer, Engel, Mueller, Hoerauf, Hübner and Schumak.)