ArticlePLoS pathogens2018
Microvesicles from malaria-infected red blood cells activate natural killer cells via MDA5 pathway.
Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
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Who cites it
44 citing papers in PubMed, 71 citations in OpenAlex.
- Activatory Receptor NKp30 Predicts NK Cell Activation During Controlled Human Malaria Infection.Frontiers in immunology · 2019Trial
- LFA-1 interaction with GBP-130 oneLife · 2026Article
- Nuclear import of malaria RNA rewires splicing in host immune cells.Cell reports · 2026Article
- NKp30: A Key Membrane Molecule in the Fight Against Cancer and Infection.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Article
- Spectral flow cytometry for detecting DNA cargo in malaria parasite-derived extracellular vesicles.The Journal of biological chemistry · 2025Article
- Host Immune Cell Membrane Deformability Governs the Uptake Route of Malaria-Derived Extracellular Vesicles.ACS nano · 2025Article
- Chloroquine induces eryptosis inFrontiers in cellular and infection microbiology · 2025Article
- Repeat controlled human Plasmodium falciparum infections delay bloodstream patency and reduce symptoms.Nature communications · 2024Article
- Extracellular Vesicles in Malaria: Shedding Light on Pathogenic Depths.ACS infectious diseases · 2024Review
- Starvation induces changes in abundance and small RNA cargo of extracellular vesicles released from Plasmodium falciparum infected red blood cells.Scientific reports · 2023Article
- Red Blood Cell-Derived Extracellular Vesicles: An Overview of Current Research Progress, Challenges, and Opportunities.Biomedicines · 2023Review
- Guidelines for the purification and characterization of extracellular vesicles of parasites.Journal of extracellular biology · 2023Article
- Comparison of infection and human immune responses of two SARS-CoV-2 strains in a humanized hACE2 NIKO mouse model.Scientific reports · 2023Article
- Biogenesis of extracellular vesicles in protozoan parasites: The ESCRT complex in the trafficking fast lane?PLoS pathogens · 2023Review
- An update on cerebral malaria for therapeutic intervention.Molecular biology reports · 2022Review
- Erythropoiesis and Malaria, a Multifaceted Interplay.International journal of molecular sciences · 2022Review
- Friend or foe: RIG- I like receptors and diseases.Autoimmunity reviews · 2022Review
- Selective expression of variant surface antigens enables Plasmodium falciparum to evade immune clearance in vivo.Nature communications · 2022Article
- Dihydroartemisinin regulates immune cell heterogeneity by triggering a cascade reaction of CDK and MAPK phosphorylation.Signal transduction and targeted therapy · 2022Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 5 countries.
Funding
Abstract
Natural killer (NK) cells provide the first line of defense against malaria parasite infection. However, the molecular mechanisms through which NK cells are activated by parasites are largely unknown, so is the molecular basis underlying the variation in NK cell responses to malaria infection in the human population. Here, we compared transcriptional profiles of responding and non-responding NK cells following exposure to Plasmodium-infected red blood cells (iRBCs) and identified MDA5, a RIG-I-like receptor involved in sensing cytosolic RNAs, to be differentially expressed. Knockout of MDA5 in responding human NK cells by CRISPR/cas9 abolished NK cell activation, IFN-γ secretion, lysis of iRBCs. Similarly, inhibition of TBK1/IKKε, an effector molecule downstream of MDA5, also inhibited activation of responding NK cells. Conversely, activation of MDA5 by liposome-packaged poly I:C restored non-responding NK cells to lyse iRBCs. We further show that microvesicles containing large parasite RNAs from iRBCs activated NK cells by fusing with NK cells. These findings suggest that NK cells are activated through the MDA5 pathway by parasite RNAs that are delivered to the cytoplasm of NK cells by microvesicles from iRBCs. The difference in MDA5 expression between responding and non-responding NK cells following exposure to iRBCs likely contributes to the variation in NK cell responses to malaria infection in the human population.
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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.