The acid ceramidase/ceramide axis controls parasitemia in Plasmodium yoelii-infected mice by regulating erythropoiesis
| Autor: | Anne Günther, Matthias Hose, Hanna Abberger, Fabian Schumacher, Ylva Veith, Burkhard Kleuser, Kai Matuschewski, Karl Sebastian Lang, Erich Gulbins, Jan Buer, Astrid M Westendorf, Wiebke Hansen |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Medizinische Fakultät » Universitätsklinikum Essen » Institut für Medizinische Mikrobiologie
ceramide -- infectious disease -- malaria -- microbiology -- mouse -- sphingolipids sphingolipids General Immunology and Microbiology Mouse Medizinische Fakultät » Universitätsklinikum Essen » Institut für Immunologie General Neuroscience Medizin malaria 500 Naturwissenschaften und Mathematik::570 Biowissenschaften Biologie::570 Biowissenschaften Biologie General Medicine General Biochemistry Genetics and Molecular Biology Medizinische Fakultät » Universitätsklinikum Essen » Institut für Molekularbiologie (Tumorforschung) parasitic diseases ddc:610 ceramide |
| Popis: | Acid ceramidase (Ac) is part of the sphingolipid metabolism and responsible for the degradation of ceramide. As bioactive molecule, ceramide is involved in the regulation of many cellular processes. However, the impact of cell-intrinsic Ac activity and ceramide on the course of Plasmodium infection remains elusive. Here, we use Ac-deficient mice with ubiquitously increased ceramide levels to elucidate the role of endogenous Ac activity in a murine malaria model. Interestingly, ablation of Ac leads to alleviated parasitemia associated with decreased T cell responses in the early phase of Plasmodium yoelii (P. yoelii) infection. Mechanistically, we identified dysregulated erythropoiesis with reduced numbers of reticulocytes, the preferred host cells of P. yoelii, in Ac-deficient mice. Furthermore, we demonstrate that administration of the Ac inhibitor carmofur to wild type mice has similar effects on P. yoelii infection and erythropoiesis. Notably, therapeutic carmofur treatment after manifestation of P. yoelii infection is efficient in reducing parasitemia. Hence, our results provide evidence for the involvement of Ac and ceramide in controlling P. yoelii infection by regulating red blood cell development. |
| Databáze: | OpenAIRE |
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