Neutrophil extracellular traps drive inflammatory pathogenesis in malaria

Knackstedt, Sebastian Lorenz, Georgiadou, Athina, Apel, Falko, Abu-Abed, Ulrike, Moxon, Christopher A, Cunnington, Aubrey J, Raupach, Baerbel, Cunningham, Deirdre, Langhorne, Jean, Krueger, Renate
et al (show 10 more authors) (2019) Neutrophil extracellular traps drive inflammatory pathogenesis in malaria. SCIENCE IMMUNOLOGY, 4 (40). eaaw0336-.

[img] Text
knackstedt et al 09112018.pdf - Author Accepted Manuscript

Download (280kB) | Preview


Neutrophils are essential innate immune cells that extrude chromatin in the form of neutrophil extracellular traps (NETs) when they die. This form of cell death has potent immunostimulatory activity. We show that heme-induced NETs are essential for malaria pathogenesis. Using patient samples and a mouse model, we define two mechanisms of NET-mediated inflammation of the vasculature: activation of emergency granulopoiesis via granulocyte colony-stimulating factor production and induction of the endothelial cytoadhesion receptor intercellular adhesion molecule-1. Soluble NET components facilitate parasite sequestration and mediate tissue destruction. We demonstrate that neutrophils have a key role in malaria immunopathology and propose inhibition of NETs as a treatment strategy in vascular infections.

Item Type: Article
Uncontrolled Keywords: Neutrophils, Animals, Mice, Knockout, Humans, Mice, Malaria, Inflammation, Extracellular Traps
Depositing User: Symplectic Admin
Date Deposited: 28 Oct 2019 09:45
Last Modified: 09 Feb 2023 02:16
DOI: 10.1126/sciimmunol.aaw0336
Related URLs: