Myeloperoxidase is required for neutrophil extracellular trap formation: implications for innate immunity.
The granule enzyme myeloperoxidase (MPO) plays an important role in neutrophil antimicrobial responses. However, the severity of immunodeficiency in patients carrying mutations in MPO is variable. Serious microbial infections, especially with Candida species, have been observed in a subset of completely MPO-deficient patients. Here we show that neutrophils from donors who are completely deficient in MPO fail to form neutrophil extracellular traps (NETs), indicating that MPO is required for NET formation. In contrast, neutrophils from partially MPO-deficient donors make NETs, and pharmacological inhibition of MPO only delays and reduces NET formation. Extracellular products of MPO do not rescue NET formation, suggesting that MPO acts cell-autonomously. Finally, NET-dependent inhibition of Candida albicans growth is compromised in MPO-deficient neutrophils. The inability to form NETs may contribute in part to the host defense defects observed in completely MPO-deficient individuals.
Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Berlin, Germany.
Kathleen D
KD
Metzler
Tobias A
TA
Fuchs
William M
WM
Nauseef
Dominique
D
Reumaux
Joachim
J
Roesler
Ilka
I
Schulze
Volker
V
Wahn
Venizelos
V
Papayannopoulos
Arturo
A
Zychlinsky
D000814:Aniline Compounds / Q000494:pharmacology; D001782:Blood Donors; D015153:Blotting, Western; D002176:Candida albicans / Q000502:physiology; D002478:Cells, Cultured; D005110:Extracellular Space / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D005838:Genotype; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D008856:Microscopy, Fluorescence; D009154:Mutation; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D009195:Peroxidase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000814:Aniline Compounds; C034343:4-aminobenzhydrazide; D009195:Peroxidase; D013755:Tetradecanoylphorbol Acetate