Neutrophil extracellular traps drive inflammatory pathogenesis in malaria
Open Access
- 11 October 2019
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Immunology
- Vol. 4 (40)
- https://doi.org/10.1126/sciimmunol.aaw0336
Abstract
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.Keywords
Funding Information
- Medical Research Council (MR/R02149X/1)
- Max Planck Society
- Western Norway Regional Health Authority
- The National Center for Tropical Medicine and Imported Infectious Diseases, Bergen, Norway
- The Medical Association for Infectious Diseases in Norway
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