Artikel
Type I interferon signalling on macrophages is involved in the immunopathology of experimental cerebral malaria
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Veröffentlicht: | 17. Dezember 2014 |
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Gliederung
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Background: Infections with Plasmodium parasites may lead to cerebral malaria (CM), which is the result of inflammatory immune responses.
Objective: We will analyse the contribution of type I IFNs in the induction of experimental CM (ECM) in the P. berghei ANKA (PbA) infection of C57BL/6 mice.
Method: We injected 5x104 infected erythrocytes of PbA parasites expressing ovalbumin (PbA-OVA) intravenously into WT mice, the genetically deficient strain IFNaR -/- and cell-type specific knock out mice i.e. LysMCRE x IFNAR flox/flox and CD11cCRE x IFNAR flox/flox. The mice were monitored for survival and scored for ECM symptoms. Blood-brain barrier (BBB) integrity was analysed by an Evan’s Blue assay. Cellular infiltrates from the brain and the spleen were isolated and stained and analysed using flow cytometry. We evaluated T cell functions by in vivo cytotoxicity assays, IFN-γ and granzyme B production.
Results: Mice lacking IFNAR on all cells or exclusively on macrophages were significantly protected against ECM and showed a stable BBB. Brains contained less infiltrated cells (T cells and other inflammatory cells) as compared to the wild type mice suffering from ECM, these infiltrated cells were also less cytotoxic which was shown by less production of granzyme B. However, the CTL responses in the spleens were unchanged.
Conclusion: Thus, we hypothesize that IFNARs have an important role in penetration of the BBB in PbA-OVA infection, but they are dispensable for the generation of specific immune responses in the periphery.
Note: The authors Patricia Korir and Janina Kuepper contributed equally.