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.