Journal Article

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

Reichwald, Julia J., Korir, Patricia Jebett, Schwendt, Kim E., Borsche, Max, Lewis, Matthew D., Thiebes, Stephanie, Engel, Daniel R., Mueller, Ann-Kristin, Hübner, Marc P., Jenster, Lea-Marie, Klocke, Katrin, Scheunemann, Johanna F., Schumak, Beatrix, Soun, Camille, Kuehlwein, Janina M., Hoerauf, Achim, Hammerschmidt-Kamper, Christiane, Limmer, Andreas

2021

Overview

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.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Animals / Animals, Outbred Strains / Anopheles - parasitology / Antigens / Antigens, Protozoan - immunology / Blood parasites / Brain - immunology / CD8 antigen / CD8 T cells / Cell Movement / Chemokine CCL5 - analysis / Chemokine CCL5 - physiology / Chemokines / Cytotoxicity / Cytotoxicity, Immunologic / eosinophils / Eosinophils - physiology / Exocrine glands / experimental cerebral malaria (ECM) / Extracellular matrix / Female / IFNAR1 / Immune response / Immunology / Infections / Leukocyte Count / Leukocyte migration / Leukocytes (eosinophilic) / Lymphocytes / Lymphocytes T / Malaria / Malaria, Cerebral - immunology / Malaria, Cerebral - parasitology / Mice / Mice, Inbred C57BL / Mice, Knockout / Mosquito Vectors - parasitology / Mosquitoes / Organisms, Genetically Modified / Ovalbumin / Parasitemia - immunology / Parasitemia - parasitology / Parasites / Pathology / Peptide Fragments / Peptides / Plasmodium berghei / Plasmodium berghei - genetics / Receptor, Interferon alpha-beta - deficiency / Receptor, Interferon alpha-beta - genetics / Receptors, CCR5 - physiology / Spleen / Spleen - chemistry / Spleen - immunology / T-Lymphocytes - immunology