ArticleScientific reports2022
Uptake of Plasmodium chabaudi hemozoin drives Kupffer cell death and fuels superinfections.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 24 citations in OpenAlex.
- RMF-Activated Superparamagnetic Iron Oxide Nanoparticles Trigger Macrophage-Dependent Protection AgainstInternational journal of molecular sciences · 2026Article
- Tissue-Resident Macrophages: Linking Physiology and Inflammation in Infection.Clinical reviews in allergy & immunology · 2026Review
- Article
- Kupffer cells in liver homeostasis and disease: from immune sentinels to metabolic gatekeepers.Nature reviews. Immunology · 2026Review
- Copper overload drives hepatic stellate cell activation via cuproptosis to exacerbate acute liver injury in murine malaria.Parasites & vectors · 2026Article
- The endemic dilemma: why whole sporozoite malaria vaccine efficacy falls in the field.Trends in parasitology · 2026Review
- Acyl-CoA Synthetase Long-Chain Family Member 4 in Liver Injury: Multidimensional Regulation and Therapeutic Potential.Gastroenterology research · 2026Review
- Hepatorenal protective role of encapsulatedJournal of advanced veterinary and animal research · 2026Article
- Kupffer cells are essential for platelet-mediated thrombopoietin generation in the liver.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Ferroptosis and gut microbiota: A new horizon in alcohol-associated liver disease management.Cellular and molecular life sciences : CMLS · 2025Review
- Emerging Molecular Mechanisms in Malaria Pathogenesis and Novel Therapeutic Approaches: A Focus onBiomolecules · 2025Review
- Hepatic ferroptosis induced by Clonorchis sinensis exacerbates liver fibrosis.PLoS neglected tropical diseases · 2025Article
- Natural hemozoin and β-hematin induce tissue damage and apoptosis in human placental explants.Toxicology reports · 2025Article
- Kupffer cell and recruited macrophage heterogeneity orchestrate granuloma maturation and hepatic immunity in visceral leishmaniasis.Nature communications · 2025Article
- Hemozoin: a waste product after heme detoxification?Parasites & vectors · 2025Article
- Transcriptome profiling of intrahepatocyticFrontiers in genetics · 2025Article
- Decoding the heterogeneity of liver-resident macrophages in chronic liver diseases: therapeutic responses to immunomodulatory strategies.Frontiers in pharmacology · 2025Review
- Heme oxygenase 1-mediated ferroptosis in Kupffer cells initiates liver injury during heat stroke.Acta pharmaceutica Sinica. B · 2024Article
- Ferroptosis in Liver Disease: Natural Active Compounds and Therapeutic Implications.Antioxidants (Basel, Switzerland) · 2024Review
- Ontogeny, functions and reprogramming of Kupffer cells upon infectious disease.Frontiers in immunology · 2023Review
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Kupffer cells (KCs) are self-maintained tissue-resident macrophages that line liver sinusoids and play an important role on host defense. It has been demonstrated that upon infection or intense liver inflammation, KCs might be severely depleted and replaced by immature monocytic cells; however, the mechanisms of cell death and the alterations on liver immunity against infections deserves further investigation. We explored the impact of acute Plasmodium infection on KC biology and on the hepatic immune response against secondary infections. Similar to patients, infection with Plasmodium chabaudi induced acute liver damage as determined by serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation. This was associated with accumulation of hemozoin, increased of proinflammatory response and impaired bacterial and viral clearance, which led to pathogen spread to other organs. In line with this, mice infected with Plasmodium had enhanced mortality during secondary infections, which was associated with increased production of mitochondrial superoxide, lipid peroxidation and increased free iron within KCs-hallmarks of cell death by ferroptosis. Therefore, we revealed that accumulation of iron with KCs, triggered by uptake of circulating hemozoin, is a novel mechanism of macrophage depletion and liver inflammation during malaria, providing novel insights on host susceptibility to secondary infections. Malaria can cause severe liver damage, along with depletion of liver macrophages, which can predispose individuals to secondary infections and enhance the chances of death.
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Registered trials
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