ArticleJournal of immunology (Baltimore, Md. : 1950)2010
Protein-DNA complex is the exclusive malaria parasite component that activates dendritic cells and triggers innate immune responses.
Article in Journal of immunology (Baltimore, Md. : 1950), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.
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Who cites it
82 citing papers in PubMed, 1 synthesis or guideline pooled it, 140 citations in OpenAlex.
- Systematic Overview of Solid Particles and Their Host Responses.Frontiers in immunology · 2018Pooled it
- Malaria-induced NLRP12/NLRP3-dependent caspase-1 activation mediates inflammation and hypersensitivity to bacterial superinfection.PLoS pathogens · 2014Trial
- Cellular and molecular interactions underlying the peripheral immune responses to blood-stage malaria infections.ImmunoHorizons · 2026Review
- mRNA vaccination overcomes haemozoin-mediated impairment of whole-parasite malaria vaccines in mice.Nature microbiology · 2026Article
- mRNA vaccination overcomes hemozoin-mediated impairment of whole parasite vaccine efficacy for malaria.bioRxiv : the preprint server for biology · 2025Article
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- Function and regulation of cGAS-STING signaling in infectious diseases.Frontiers in immunology · 2023Review
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- Altered Cytokine Response of Human Brain Endothelial Cells after Stimulation with Malaria Patient Plasma.Cells · 2021Article
- Broader Insights into Understanding Tumor Necrosis Factor and Neurodegenerative Disease Pathogenesis Infer New Therapeutic Approaches.Journal of Alzheimer's disease : JAD · 2021Review
- TLR-9 Plays a Role inFrontiers in immunology · 2021Article
- Caspase-8 mediates inflammation and disease in rodent malaria.Nature communications · 2020Article
- RTP4 inhibits IFN-I response and enhances experimental cerebral malaria and neuropathology.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Type I Interferons and Malaria: A Double-Edge Sword Against a Complex Parasitic Disease.Frontiers in cellular and infection microbiology · 2020Review
- Role of Extracellular Vesicles in Cellular Cross Talk in Malaria.Frontiers in immunology · 2020Review
- Innate immunity to malaria-The role of monocytes.Immunological reviews · 2020Review
- Plasmodium-specific antibodies block in vivo parasite growth without clearing infected red blood cells.PLoS pathogens · 2019Article
- Chronic TLR7 and TLR9 signaling drives anemia via differentiation of specialized hemophagocytes.Science (New York, N.Y.) · 2019Article
- Different Life Cycle Stages ofFrontiers in immunology · 2019Article
- Dendritic Cell Responses and Function in Malaria.Frontiers in immunology · 2019Review
22 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Dendritic cells (DCs) play a crucial role in the development of protective immunity to malaria. However, it remains unclear how malaria parasites trigger immune responses in DCs. In this study, we purified merozoites, food vacuoles, and parasite membrane fragments released during the Plasmodium falciparum schizont burst to homogeneity and tested for the activation of bone marrow-derived DCs from wild-type and TLR2(-/-), TLR4(-/-), TLR9(-/-), and MyD88(-/-) C57BL/6J mice. The results demonstrate that a protein-DNA complex is the exclusive parasite component that activates DCs by a TLR9-dependent pathway to produce inflammatory cytokines. Complex formation with proteins is essential for the entry of parasite DNA into DCs for TLR9 recognition and, thus, proteins convert inactive DNA into a potent immunostimulatory molecule. Exogenous cationic polymers, polylysine and chitosan, can impart stimulatory activity to parasite DNA, indicating that complex formation involves ionic interactions. Merozoites and DNA-protein complex could also induce inflammatory cytokine responses in human blood DCs. Hemozoin is neither a TLR9 ligand for DCs nor functions as a carrier of DNA into cells. Additionally, although TLR9 is critical for DCs to induce the production of IFN-gamma by NK cells, this receptor is not required for NK cells to secret IFN-gamma, and cell-cell contact among myeloid DCs, plasmacytoid DCs, and NK cells is required for IFN-gamma production. Together, these results contribute substantially toward the understanding of malaria parasite-recognition mechanisms. More importantly, our finding that proteins and carbohydrate polymers are able to confer stimulatory activity to an otherwise inactive parasite DNA have important implications for the development of a vaccine against malaria.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.