Neutrophil extracellular traps drive inflammatory pathogenesis in malaria

Sebastian Lorenz Knackstedt, Athina Georgiadou, Falko Apel, Ulrike Abu-Abed, Christopher A Moxon, Aubrey J Cunnington, Bärbel Raupach, Deirdre Cunningham, Jean Langhorne, Renate Krüger, Valentina Barrera, Simon P Harding, Aase Berg, Sam Patel, Kari Otterdal, Benjamin Mordmüller, Evelin Schwarzer, Volker Brinkmann, Arturo Zychlinsky, Borko Amulic

Research output: Contribution to journalArticle (Academic Journal)peer-review

21 Citations (Scopus)
133 Downloads (Pure)

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.

Original languageEnglish
Article numbereaaw0336
Number of pages18
JournalScience Immunology
Volume4
Issue number40
DOIs
Publication statusPublished - 18 Oct 2019

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