The differential effect of Interferon-gamma on acute kidney injury and parasitemia in experimental malaria
Abstract Malaria-associated acute kidney injury (MAKI) is a common complication of Plasmodium infection, affecting ~ 50% of severe malaria cases and associated with increased mortality. However, its immunopathogenesis remains unclear. Interferon-gamma (IFN-gamma) is a crucial cytokine that influence...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-02-01
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| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-90473-7 |
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| Summary: | Abstract Malaria-associated acute kidney injury (MAKI) is a common complication of Plasmodium infection, affecting ~ 50% of severe malaria cases and associated with increased mortality. However, its immunopathogenesis remains unclear. Interferon-gamma (IFN-gamma) is a crucial cytokine that influences parasite clearance and mediates pathogenesis in experimental models of malaria. This study explored the role of IFN-gamma in kidney pathology in C57BL/6 mice infected with Plasmodium berghei NK65 (PbNK65) and P. chabaudi AS (PcAS). PbNK65-infected mice, normally susceptible to severe malaria, were protected from both MAKI and malaria-associated acute respiratory distress syndrome (MA-ARDS) when lacking IFN-gamma. Infected IFN-gamma knockout (KO) mice developed low parasitemia levels, minimal kidney histopathological changes and reduced expression of the kidney injury marker Neutrophil Gelatinase-Associated Lipocalin (NGAL). In contrast, upon PcAS-infection, IFN-gamma deficiency led to increased parasitemia and aggravated kidney pathology, evidenced by proteinuria, hyaline casts in kidneys and increased renal mRNA expression of Heme Oxygenase 1 (HO-1) and NGAL. In both models, IFN-gamma induced renal C-X-C Motif Chemokine Ligand 10 (CXCL10) but did not affect Tumor Necrosis Factor-alpha (TNF-alpha) expression. Our data indicate that IFN-gamma exerts a dual effect on kidney pathology, which is conditioned by the mouse model and its impact on parasitemia. |
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| ISSN: | 2045-2322 |