Article
CD8a+ dendritic cells in the pathogenesis of experimental cerebral malaria
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Authors
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Max Borsche
- Institute of Medical Microbiology, Immunology and Parasitology, University Clinic, Bonn, Germany
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Janina M. Kuepper
- Institute of Medical Microbiology, Immunology and Parasitology, University Clinic, Bonn, Germany
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Achim Hoerauf
- Institute of Medical Microbiology, Immunology and Parasitology, University Clinic, Bonn, Germany
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Ildiko R. Dunay
- Institute of Medical Microbiology, University Clinic, Magdeburg, Germany
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Beatrix Schumak
- Institute of Medical Microbiology, Immunology and Parasitology, University Clinic, Bonn, Germany
| Published: | December 17, 2014 |
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Outline
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1. Introduction: Cerebral Malaria (CM) is a life-threatening complication of infection with Plasmodium falciparum and is caused by a combination of brain-sequestered parasites and cerebral inflammation. However, the exact mechanism how P. falciparum infection leads to CM and why it only occurs in some cases remains unclear.
Studies in murine models have shown that CD8+ cytotoxic T cells are essential for the development of experimental cerebral malaria (ECM). However, T cells need co-stimulation from antigen-presenting cells to perform proper effector functions. CD8+ DCs are important for T cell priming and are described as highly relevant cells in cross-presenting antigens via MHC class I to CD8+ T cells. In this study we want to evaluate the impact of CD8+ dendritic cells (DCs) in the development of ECM in P. berghei ANKA (PbA) infected C57BL/6 mice.
2. Materials & methods: C57BL/6 wt mice and Batf3 ko mice (genetically lack CD8+ DCs) were intravenously infected with blood stages of PbA and analyzed for disease development or sacrificed for ex vivo analysis when first cerebral symptoms were obvious (day 6 post infection). Spleen and brain of infected animals were analyzed for cell composition via FACS and cytokine production with ELISA.
3. Results: We showed that Batf3 ko mice do not succumb to ECM upon infection with PbA. In these mice the inflammation was significantly decreased as shown by generally reduced immune cell infiltration and down regulation of several activation markers on immune cells in the brains. The adhesion molecule ICAM-1 was reduced on T cells from brain and spleen. Although splenic T cells were still able to eliminate antigen labeled cells in an in vivo cytotoxicity assay, they differed in the production of granzyme B.
4. Conclusion: These results lead to the assumption that the priming environment in Batf3 ko mice differs dramatically from wild type mice, as different T cell effector populations arise which may be responsible for the protection of Batf3 ko mice against ECM upon PbA infection. The decrease of ICAM-1 expression on T cells might additionally contribute to the protection as cell adhesion in the blood vessels could be reduced. This needs to be validated in future experiments.
Note: The authors Max Borsche and Janina M. Kuepper contributed equally.
