CXCR4 and MIF are required for neutrophil extracellular trap release triggered by Plasmodium-infected erythrocytes

Autor: Pedro M. Pimentel-Coelho, José M. C. Ribeiro, Elvira M. Saraiva, Alassane Dicko, Andreza Moreira Gama, Heitor A. Paula-Neto, Heitor S. de Souza, Ivo M.B. Francischetti, Leandro S. Silva, Danielle A. S. Rodrigues, Patrick E. Duffy, Ana Acacia S. Pinheiro, Elisa Beatriz Prestes, Raquel Maria Pereira Campos, Michal Fried, Marcelo T. Bozza
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Plasmodium
Erythrocytes
Neutrophils
Hydrolases
Parasitemia
CXCR4
Biochemistry
Extracellular Traps
Chemokine receptor
White Blood Cells
Mice
Medical Conditions
Animal Cells
Red Blood Cells
Medicine and Health Sciences
Biology (General)
Protozoans
0303 health sciences
Deoxyribonucleases
biology
Chemistry
030302 biochemistry & molecular biology
Malarial Parasites
Eukaryota
Animal Models
Enzymes
Histone citrullination
Experimental Organism Systems
Neutrophil elastase
Myeloperoxidase
Cellular Types
Research Article
Receptors
CXCR4
QH301-705.5
Nucleases
Immune Cells
Immunology
Mouse Models
Research and Analysis Methods
Microbiology
03 medical and health sciences
Model Organisms
Virology
parasitic diseases
Parasite Groups
DNA-binding proteins
Genetics
medicine
Parasitic Diseases
Animals
Humans
Molecular Biology
Macrophage Migration-Inhibitory Factors
030304 developmental biology
Blood Cells
Organisms
Biology and Life Sciences
Proteins
Neutrophil extracellular traps
Cell Biology
RC581-607
medicine.disease
Tropical Diseases
Parasitic Protozoans
Malaria
Mice
Inbred C57BL
biology.protein
Enzymology
Animal Studies
Macrophage migration inhibitory factor
Parasitology
Immunologic diseases. Allergy
Apicomplexa
Zdroj: PLoS Pathogens
PLoS Pathogens, Vol 16, Iss 8, p e1008230 (2020)
ISSN: 1553-7374
1553-7366
Popis: Neutrophil extracellular traps (NETs) evolved as a unique effector mechanism contributing to resistance against infection that can also promote tissue damage in inflammatory conditions. Malaria infection can trigger NET release, but the mechanisms and consequences of NET formation in this context remain poorly characterized. Here we show that patients suffering from severe malaria had increased amounts of circulating DNA and increased neutrophil elastase (NE) levels in plasma. We used cultured erythrocytes and isolated human neutrophils to show that Plasmodium-infected red blood cells release macrophage migration inhibitory factor (MIF), which in turn caused NET formation by neutrophils in a mechanism dependent on the C-X-C chemokine receptor type 4 (CXCR4). NET production was dependent on histone citrullination by peptidyl arginine deiminase-4 (PAD4) and independent of reactive oxygen species (ROS), myeloperoxidase (MPO) or NE. In vitro, NETs functioned to restrain parasite dissemination in a mechanism dependent on MPO and NE activities. Finally, C57/B6 mice infected with P. berghei ANKA, a well-established model of cerebral malaria, presented high amounts of circulating DNA, while treatment with DNAse increased parasitemia and accelerated mortality, indicating a role for NETs in resistance against Plasmodium infection.
Author summary Protozoans of the Plasmodium genre infect red blood cells and cause malaria in humans and various other mammalian species. Estimated malaria cases are at more than 200 million, with 450,000 deaths per year, being cerebral malaria a serious complication that accounts for the majority of deaths. Neutrophils are cells that participate in host defense against pathogens. These cells use various mechanisms to kill invading microrganisms, including the release of webs of DNA, called neutrophil extracellular traps (NETs). These NETs can help control infections but can also induce tissue damage and their role in malaria and the mechanisms of NET production during malaria infection are starting to be understood. Here we show that infected red blood cells produce a cytokine, macrophage migration inhibitory factor (MIF) that stimulates neutrophils to release NETs. These NETs function to limit Plasmodium dissemination and, thus, digestion of NETs with DNAse treatment causes increased parasitemia and accelerated death in an experimental model of cerebral malaria. Our study uncovers the mechanism by which infected red blood cells stimulate neutrophils to release NETs and suggest an important participation of this process in malaria control.
Databáze: OpenAIRE
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