Neutrophil extracellular traps drive inflammatory pathogenesis in malaria

被引：121

作者：

Knackstedt, Sebastian Lorenz ^{[1
]}

Georgiadou, Athina ^{[2
]}

Apel, Falko ^{[1
]}

Abu-Abed, Ulrike ^{[3
]}

Moxon, Christopher A. ^{[4
,5
]}

Cunnington, Aubrey J. ^{[2
]}

Raupach, Baerbel ^{[1
]}

Cunningham, Deirdre ^{[6
]}

Langhorne, Jean ^{[6
]}

Krueger, Renate ^{[7
,8
]}

Barrera, Valentina ^{[9
]}

Harding, Simon P. ^{[9
]}

Berg, Aase ^{[10
]}

Patel, Sam ^{[11
]}

Otterdal, Kari ^{[12
]}

Mordmueller, Benjamin ^{[13
,14
]}

Schwarzer, Evelin ^{[15
]}

Brinkmann, Volker ^{[3
]}

Zychlinsky, Arturo ^{[1
]}

Amulic, Borko ^{[1
,16
]}

机构：

[1] Max Planck Inst Infect Biol, Dept Cellular Microbiol, Charitepl 1, D-10117 Berlin, Germany

[2] Imperial Coll London, Sect Paediat, London W21 PG, England

[3] Max Planck Inst Infect Biol, Microscopy Core Facil, Charitepl 1, D-10117 Berlin, Germany

[4] Univ Glasgow, Inst Infect Immun & Inflammat, Wellcome Ctr Integrat Parasitol, Glasgow, Lanark, Scotland

[5] Univ Liverpool, Inst Infect & Global Hlth, 8 West Derby St, Liverpool L69 7BE, Merseyside, England

[6] Francis Crick Inst, 1 Midland Rd, London NW1 1AT, England

[7] Humboldt Univ, Charite Univ Med Berlin, Berlin, Germany

[8] Berlin Inst Hlth, Dept Pediat Pneumol Immunol & Intens Care, Berlin, Germany

[9] Univ Liverpool, Inst Ageing & Chron Dis, Dept Eye & Vis Sci, Liverpool, Merseyside, England

[10] Stavanger Univ Hosp, Stavanger, Norway

[11] Maputo Cent Hosp, Maputo, Mozambique

[12] Oslo Univ Hosp, Rikshosp, Res Inst Internal Med, Oslo, Norway

[13] Ctr Rech Med Lambarene CERMEL, Lambarene, Gabon

[14] Univ Tubingen, Inst Tropenmed, Wilhelmstr 27, D-72074 Tubingen, Germany

[15] Univ Turin, Dept Oncol, Via Santena 5 Bis, I-10126 Turin, Italy

[16] Univ Bristol, Sch Cellular & Mol Med, Bristol BS8 1TD, Avon, England

来源：

SCIENCE IMMUNOLOGY | 2019年 / 4卷 / 40期

基金：

英国医学研究理事会;

关键词：

PLASMODIUM-FALCIPARUM MALARIA; INTERCELLULAR-ADHESION MOLECULE-1; CEREBRAL MALARIA; HEMATOLOGICAL PARAMETERS; CYTOKINE PRODUCTION; CHABAUDI MALARIA; ACTIVATION; PARASITE; HOST; HEME;

D O I：

10.1126/sciimmunol.aaw0336

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页数：17

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