ArticlePloS one2011
The nucleosome (histone-DNA complex) is the TLR9-specific immunostimulatory component of Plasmodium falciparum that activates DCs.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 55 citations in OpenAlex.
- Circulating Nucleosomes as a Novel Biomarker for Sepsis: A Scoping Review.Biomedicines · 2024Article
- Steatotic Donor Transplant Livers: Preservation Strategies to Mitigate against Ischaemia-Reperfusion Injury.International journal of molecular sciences · 2024Review
- Nanoparticulate cell-free DNA scavenger for treating inflammatory bone loss in periodontitis.Nature communications · 2022Article
- Innate immunity to malaria: The good, the bad and the unknown.Frontiers in immunology · 2022Review
- Signaling pathways and intervention therapies in sepsis.Signal transduction and targeted therapy · 2021Review
- TLR-9 Plays a Role inFrontiers in immunology · 2021Article
- Innate immunity to malaria-The role of monocytes.Immunological reviews · 2020Review
- Type I Interferons and Malaria: A Double-Edge Sword Against a Complex Parasitic Disease.Frontiers in cellular and infection microbiology · 2020Review
- Modulation of toll-like receptor signaling by antimicrobial peptides.Seminars in cell & developmental biology · 2019Review
- A malaria protein factor induces IL-4 production by dendritic cells via PI3K-Akt-NF-κB signaling independent of MyD88/TRIF and promotes Th2 response.The Journal of biological chemistry · 2018Article
- Review
- Red Blood Cells Homeostatically Bind Mitochondrial DNA through TLR9 to Maintain Quiescence and to Prevent Lung Injury.American journal of respiratory and critical care medicine · 2018Article
- Cyclic GMP-AMP Synthase Is the Cytosolic Sensor ofJournal of immunology (Baltimore, Md. : 1950) · 2018Article
- Parasite Recognition and Signaling Mechanisms in Innate Immune Responses to Malaria.Frontiers in immunology · 2018Review
- Extracellular histones, cell-free DNA, or nucleosomes: differences in immunostimulation.Cell death & disease · 2016Review
- Monocyte activation and cytokine production in Malawian children presenting with P. falciparum malaria.Parasite immunology · 2016Article
- Loss of Toll-like receptor 7 alters cytokine production and protects against experimental cerebral malaria.Malaria journal · 2014Article
- NLR proteins and parasitic disease.Immunologic research · 2014Review
- Malarial hemozoin: from target to tool.Biochimica et biophysica acta · 2014Review
- A surprising role for uric acid: the inflammatory malaria response.Current rheumatology reports · 2014Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The systemic clinical symptoms of Plasmodium falciparum infection such as fever and chills correspond to the proinflammatory cytokines produced in response to the parasite components released during the synchronized rupture of schizonts. We recently demonstrated that, among the schizont-released products, merozoites are the predominant components that activate dendritic cells (DCs) by TLR9-specific recognition to induce the maturation of cells and to produce proinflammatory cytokines. We also demonstrated that DNA is the active constituent and that formation of a DNA-protein complex is essential for the entry of parasite DNA into cells for recognition by TLR9. However, the nature of endogenous protein-DNA complex in the parasite is not known. In this study, we show that parasite nucleosome constitute the major protein-DNA complex involved in the activation of DCs by parasite nuclear material. The parasite components were fractionated into the nuclear and non-nuclear materials. The nuclear material was further fractionated into chromatin and the proteins loosely bound to chromatin. Polynucleosomes and oligonucleosomes were prepared from the chromatin. These were tested for their ability to activate DCs obtained by the FLT3 ligand differentiation of bone marrow cells from the wild type, and TLR2(-/-), TLR9(-/-) and MyD88(-/-) mice. DCs stimulated with the nuclear material and polynucleosomes as well as mono- and oligonucleosomes efficiently induced the production of proinflammatory cytokines in a TLR9-dependent manner, demonstrating that nucleosomes (histone-DNA complex) represent the major TLR9-specific DC-immunostimulatory component of the malaria parasite nuclear material. Thus, our data provide a significant insight into the activation of DCs by malaria parasites and have important implications for malaria vaccine development.
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Registered trials
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