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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Nature Portfolio
2025-02-01
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| Online Access: | https://doi.org/10.1038/s41598-025-90473-7 |
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| author | Rebecca Sadler Hendrik Possemiers Fran Prenen Lotte Van Landschoot Emilie Pollenus Margot Deckers Sofie Knoops Priyanka Koshy Patrick Matthys Philippe E. Van den Steen |
| author_facet | Rebecca Sadler Hendrik Possemiers Fran Prenen Lotte Van Landschoot Emilie Pollenus Margot Deckers Sofie Knoops Priyanka Koshy Patrick Matthys Philippe E. Van den Steen |
| author_sort | Rebecca Sadler |
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| description | 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. |
| format | Article |
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| publishDate | 2025-02-01 |
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| spelling | doaj-art-a3e50efbe28c4e61807d88b4b50ecd8c2025-08-20T02:14:59ZengNature PortfolioScientific Reports2045-23222025-02-0115111210.1038/s41598-025-90473-7The differential effect of Interferon-gamma on acute kidney injury and parasitemia in experimental malariaRebecca Sadler0Hendrik Possemiers1Fran Prenen2Lotte Van Landschoot3Emilie Pollenus4Margot Deckers5Sofie Knoops6Priyanka Koshy7Patrick Matthys8Philippe E. Van den Steen9Laboratory of Immunoparasitology, Department of Microbiology, Immunology and Transplantation, Rega Institute of Medical Research, KU LeuvenLaboratory of Immunoparasitology, Department of Microbiology, Immunology and Transplantation, Rega Institute of Medical Research, KU LeuvenLaboratory of Immunoparasitology, Department of Microbiology, Immunology and Transplantation, Rega Institute of Medical Research, KU LeuvenLaboratory of Immunoparasitology, Department of Microbiology, Immunology and Transplantation, Rega Institute of Medical Research, KU LeuvenLaboratory of Immunoparasitology, Department of Microbiology, Immunology and Transplantation, Rega Institute of Medical Research, KU LeuvenLaboratory of Immunoparasitology, Department of Microbiology, Immunology and Transplantation, Rega Institute of Medical Research, KU LeuvenLaboratory of Immunoparasitology, Department of Microbiology, Immunology and Transplantation, Rega Institute of Medical Research, KU LeuvenDepartment of Pathology, University Hospitals LeuvenLaboratory of Immunobiology, Department of Microbiology, Immunology and Transplantation, Rega Institute of Medical Research, KU LeuvenLaboratory of Immunoparasitology, Department of Microbiology, Immunology and Transplantation, Rega Institute of Medical Research, KU LeuvenAbstract 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.https://doi.org/10.1038/s41598-025-90473-7MalariaIFN-γAcute kidney injuryInflammation |
| spellingShingle | Rebecca Sadler Hendrik Possemiers Fran Prenen Lotte Van Landschoot Emilie Pollenus Margot Deckers Sofie Knoops Priyanka Koshy Patrick Matthys Philippe E. Van den Steen The differential effect of Interferon-gamma on acute kidney injury and parasitemia in experimental malaria Scientific Reports Malaria IFN-γ Acute kidney injury Inflammation |
| title | The differential effect of Interferon-gamma on acute kidney injury and parasitemia in experimental malaria |
| title_full | The differential effect of Interferon-gamma on acute kidney injury and parasitemia in experimental malaria |
| title_fullStr | The differential effect of Interferon-gamma on acute kidney injury and parasitemia in experimental malaria |
| title_full_unstemmed | The differential effect of Interferon-gamma on acute kidney injury and parasitemia in experimental malaria |
| title_short | The differential effect of Interferon-gamma on acute kidney injury and parasitemia in experimental malaria |
| title_sort | differential effect of interferon gamma on acute kidney injury and parasitemia in experimental malaria |
| topic | Malaria IFN-γ Acute kidney injury Inflammation |
| url | https://doi.org/10.1038/s41598-025-90473-7 |
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