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Malaria-derived hemozoin skews dendritic cell responses to bacterial infections by reducing interferon gene-transcription by SWI/SNF-NuRD
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.ORCID iD: 0000-0002-2321-9369
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.ORCID iD: 0000-0003-4810-2076
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.ORCID iD: 0009-0006-0599-3285
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.ORCID iD: 0000-0001-7757-7295
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Number of Authors: 102025 (English)In: iScience, E-ISSN 2589-0042, Vol. 28, no 8, article id 113046Article in journal (Refereed) Published
Abstract [en]

Hemozoin (HZ), the malaria pigment, is associated with the disease when released during the pro-inflammatory blood stage and co-infections with bacteria lead to a more severe disease progression. The underlying mechanisms are poorly understood and, here, we show that the impact of co-exposure to HZ and lipopolysaccharide (LPS) on monocyte-derived dendritic cells (moDC) alters the early transcriptional response to a subset of IFNγ controlled genes, HLA-DR, and PD-L1. HZ-exposure had no effect on inflammatory genes, which were substantially induced by LPS. The reduced expression of HLA-DR and PD-L1 by HZ was associated with the chromatin remodeling complex NuRD and a decreased binding of the NF-κB transcription factor RELA compared to cells stimulated with LPS alone. NuRD replaced the SWI/SNF complex variant PBAF at the specific promoters, without chromatin accessibility changes. The immune modulatory effect of HZ may lead to changed immune responses to bacterial co-infections.

Place, publisher, year, edition, pages
2025. Vol. 28, no 8, article id 113046
Keywords [en]
Parasitology, Immune response, Molecular mechanism of gene regulation
National Category
Immunology in the Medical Area
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URN: urn:nbn:se:su:diva-245664DOI: 10.1016/j.isci.2025.113046ISI: 001541136600001Scopus ID: 2-s2.0-105010872438OAI: oai:DiVA.org:su-245664DiVA, id: diva2:1990831
Available from: 2025-08-21 Created: 2025-08-21 Last updated: 2025-08-21Bibliographically approved

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Lasaviciute, GintareTariq, KanwalSugathan, AnaswaraQuin, JaclynPolenkowski, MareikeBujila, IoanaTroye-Blomberg, MaritaSverremark-Ekström, EvaÖstlund Farrants, Ann-Kristin

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Lasaviciute, GintareTariq, KanwalSugathan, AnaswaraQuin, JaclynPolenkowski, MareikeBujila, IoanaTroye-Blomberg, MaritaSverremark-Ekström, EvaÖstlund Farrants, Ann-Kristin
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Department of Molecular Biosciences, The Wenner-Gren Institute
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