Neutrophil extracellular traps drive inflammatory pathogenesis in malaria

Knackstedt, S. L. et al. (2019) Neutrophil extracellular traps drive inflammatory pathogenesis in malaria. Science Immunology, 4(40), eaaw0336. (doi: 10.1126/sciimmunol.aaw0336) (PMID:31628160)

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.

• Item Type: Articles
• Additional Information: Funding: B.A. is an MRC Career Development Fellow. A.J.C. was supported by MRC and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and is also part of the EDCTP2 program supported by the European Union (MR/L006529/1 to A.J.C.). A.G. was supported by an Imperial College Dean’s Internship Award. The Francis Crick Institute receives its core funding from the UK Medical Research Council (FC10101), Cancer Research UK (FC001101), and Wellcome (FC001101). J.L. is a Wellcome Senior Investigator (WT102907MA).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Moxon, Dr Christopher
• Authors: Knackstedt, S. L., Georgiadou, A., Apel, F., Abu-Abed, U., Moxon, C. A., Cunnington, A. J., Raupach, B., Cunningham, D., Langhorne, J., Krüger, R., Barrera, V., Harding, S. P., Berg, A., Patel, S., Otterdal, K., Mordmüller, B., Schwarzer, E., Brinkmann, V., Zychlinsky, A., and Amulic, B.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Science Immunology
• Publisher: American Association for the Advancement of Science
• ISSN: 2470-9468
• ISSN (Online): 2470-9468
• Published Online: 18 October 2019
• Copyright Holders: Copyright © 2019 The Authors
• First Published: First published in Science Immunology 4(40):eaaw0336
• Publisher Policy: Reproduced in accordance with the publisher copyright policy