1. Protection of Batf3-deficient mice from experimental cerebral malaria correlates with impaired cytotoxic T-cell responses and immune regulation.
- Author
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Kuehlwein JM, Borsche M, Korir PJ, Risch F, Mueller AK, Hübner MP, Hildner K, Hoerauf A, Dunay IR, and Schumak B
- Subjects
- Animals, Basic-Leucine Zipper Transcription Factors genetics, Blood-Brain Barrier immunology, Blood-Brain Barrier parasitology, Brain metabolism, Brain parasitology, Cells, Cultured, Dendritic Cells metabolism, Dendritic Cells parasitology, Disease Models, Animal, Female, Granzymes immunology, Granzymes metabolism, Host-Parasite Interactions, Interferon-gamma immunology, Interferon-gamma metabolism, Interleukin-10 immunology, Interleukin-10 metabolism, Malaria, Cerebral immunology, Malaria, Cerebral metabolism, Malaria, Cerebral parasitology, Mice, Inbred C57BL, Mice, Knockout, Plasmodium berghei immunology, Repressor Proteins genetics, Spleen immunology, Spleen metabolism, Spleen parasitology, T-Lymphocytes, Cytotoxic metabolism, T-Lymphocytes, Cytotoxic parasitology, Basic-Leucine Zipper Transcription Factors deficiency, Brain immunology, Dendritic Cells immunology, Malaria, Cerebral prevention & control, Plasmodium berghei pathogenicity, Repressor Proteins deficiency, T-Lymphocytes, Cytotoxic immunology
- Abstract
Excessive inflammatory immune responses during infections with Plasmodium parasites are responsible for severe complications such as cerebral malaria (CM) that can be studied experimentally in mice. Dendritic cells (DCs) activate cytotoxic CD8
+ T-cells and initiate immune responses against the parasites. Batf3-/- mice lack a DC subset, which efficiently induces strong CD8 T-cell responses by cross-presentation of exogenous antigens. Here we show that Batf3-/- mice infected with Plasmodium berghei ANKA (PbA) were protected from experimental CM (ECM), characterized by a stable blood-brain barrier (BBB) and significantly less infiltrated peripheral immune cells in the brain. Importantly, the absence of ECM in Batf3-/- mice correlated with attenuated responses of cytotoxic T-cells, as their parasite-specific lytic activity as well as the production of interferon gamma and granzyme B were significantly decreased. Remarkably, spleens of ECM-protected Batf3-/- mice had elevated levels of regulatory immune cells and interleukin 10. Thus, protection from ECM in PbA-infected Batf3-/- mice was associated with the absence of strong CD8+ T-cell activity and induction of immunoregulatory mediators and cells., (© 2019 The Authors. Immunology Published by John Wiley & Sons Ltd.)- Published
- 2020
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