ArticlePLoS pathogens2014
Plasmodium falciparum infection induces expression of a mosquito salivary protein (Agaphelin) that targets neutrophil function and inhibits thrombosis without impairing hemostasis.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Detection of Plasmodium in Anopheles spp (Diptera: Nematocera: Culicidae) using molecular biology techniques: a systematic review.Revista do Instituto de Medicina Tropical de Sao Paulo · 2025Pooled it
- Avian malaria and the overlooked metabolic pathways underlying mosquitoRoyal Society open science · 2025Article
- Beyond the bite: how mosquito salivary proteins modulate midgut biology and malaria parasite transmission.Current opinion in insect science · 2025Review
- The Role of Thrombo-inflammation in Ischemic Stroke: Focus on the Manipulation and Clinical Application.Molecular neurobiology · 2025Review
- Plancitoxin-1 mediates extracellular trap evasion by the parasitic helminth Trichinella spiralis.BMC biology · 2024Article
- Association of the immediate perioperative dynamics of circulating DNA levels and neutrophil extracellular traps formation in cancer patients.Precision clinical medicine · 2024Article
- Neutrophils versus Protozoan Parasites:Microorganisms · 2024Review
- An early warning indicator of mortality risk in patients with COVID-19: the neutrophil extracellular traps/neutrophilic segmented granulocyte ratio.Frontiers in immunology · 2024Article
- A Non-Coding Fc Gamma Receptor Cis-Regulatory Variant within the 1q23 Gene Cluster Is Associated withInternational journal of molecular sciences · 2023Article
- Escaping the enemy's bullets: an update on how malaria parasites evade host immune response.Parasitology research · 2023Review
- Neutrophil Extracellular Traps in Cerebral Ischemia/Reperfusion Injury: Friend and Foe.Current neuropharmacology · 2023Review
- Association of neutrophil extracellular traps with the production of circulating DNA in patients with colorectal cancer.iScience · 2022Article
- Shrew's venom quickly causes circulation disorder, analgesia and hypokinesia.Cellular and molecular life sciences : CMLS · 2022Article
- Host-parasite interactions duringFrontiers in immunology · 2022Review
- A prospective marker for the prediction of postoperative deep venous thrombosis: Neutrophil extracellular traps.Frontiers in cell and developmental biology · 2022Article
- Elastase inhibitor agaphelin protects from acute ischemic stroke in mice by reducing thrombosis, blood-brain barrier damage, and inflammation.Brain, behavior, and immunity · 2021Article
- Using two phases of the CD4 T cell response to blood-stage murine malaria to understand regulation of systemic immunity and placental pathology in Plasmodium falciparum infection.Immunological reviews · 2020Review
- Review
- A bite to fight: front-line innate immune defenses against malaria parasites.Pathogens and global health · 2018Review
- Neutrophils and Malaria.Frontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundInvasion of mosquito salivary glands (SGs) by Plasmodium falciparum sporozoites is an essential step in the malaria life cycle. How infection modulates gene expression, and affects hematophagy remains unclear. PRINCIPAL
findingsUsing Affimetrix chip microarray, we found that at least 43 genes are differentially expressed in the glands of Plasmodium falciparum-infected Anopheles gambiae mosquitoes. Among the upregulated genes, one codes for Agaphelin, a 58-amino acid protein containing a single Kazal domain with a Leu in the P1 position. Agaphelin displays high homology to orthologs present in Aedes sp and Culex sp salivary glands, indicating an evolutionarily expanded family. Kinetics and surface plasmon resonance experiments determined that chemically synthesized Agaphelin behaves as a slow and tight inhibitor of neutrophil elastase (K(D) ∼ 10 nM), but does not affect other enzymes, nor promotes vasodilation, or exhibit antimicrobial activity. TAXIscan chamber assay revealed that Agaphelin inhibits neutrophil chemotaxis toward fMLP, affecting several parameter associated with cell migration. In addition, Agaphelin reduces paw edema formation and accumulation of tissue myeloperoxidase triggered by injection of carrageenan in mice. Agaphelin also blocks elastase/cathepsin-mediated platelet aggregation, abrogates elastase-mediated cleavage of tissue factor pathway inhibitor, and attenuates neutrophil-induced coagulation. Notably, Agaphelin inhibits neutrophil extracellular traps (NETs) formation and prevents FeCl3-induced arterial thrombosis, without impairing hemostasis.
conclusionsBlockade of neutrophil elastase emerges as a novel antihemostatic mechanism in hematophagy; it also supports the notion that neutrophils and the innate immune response are targets for antithrombotic therapy. In addition, Agaphelin is the first antihemostatic whose expression is induced by Plasmodium sp infection. These results suggest that an important interplay takes place in parasite-vector-host interactions.
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