Candida albicans triggers NADPH oxidase-independent neutrophil extracellular traps through dectin-2


Autoři: Sheng-Yang Wu aff001;  Chia-Lin Weng aff001;  Min-Jhen Jheng aff001;  Hung-Wei Kan aff002;  Sung-Tsang Hsieh aff002;  Fu-Tong Liu aff003;  Betty A. Wu-Hsieh aff001
Působiště autorů: Graduate Institute of Immunology, National Taiwan University College of Medicine, Taipei, Taiwan aff001;  Department of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan aff002;  Institute of Biomedical Science, Academia Sinica, Taipei, Taiwan aff003
Vyšlo v časopise: Candida albicans triggers NADPH oxidase-independent neutrophil extracellular traps through dectin-2. PLoS Pathog 15(11): e1008096. doi:10.1371/journal.ppat.1008096
Kategorie: Research Article
doi: 10.1371/journal.ppat.1008096

Souhrn

Candida albicans is one of the top leading causes of healthcare-associated bloodstream infection. Neutrophil extracellular traps (NET) are known to capture and kill pathogens. It is reported that opsonized C. albicans-triggered NETosis is NADPH oxidase-dependent. We discovered a NADPH oxidase-independent NETosis pathway in neutrophil response to unopsonized C. albicans. While CR3 engagement with opsonized C. albicans triggered NET, dectin-2 recognized unopsonized C. albicans and mediated NET formation. Engagement of dectin-2 activated the downstream Syk-Ca2+-PKCδ-protein arginine deiminase 4 (PAD4) signaling pathway which modulated nuclear translocation of neutrophil elastase (NE), histone citrullination and NETosis. In a C. albicans peritonitis model we observed Ki67+Ly6G+ NETotic cells in the peritoneal exudate and mesenteric tissues within 3 h of infection. Treatment with PAD4 inhibitor GSK484 or dectin-2 deficiency reduced % Ki67+Ly6G+ cells and the intensity of Ki67 in peritoneal neutrophils. Employing DNA digestion enzyme micrococcal nuclease, GSK484 as well as dectin-2-deficient mice, we further showed that dectin-2-mediated PAD4-dependent NET formation in vivo restrained the spread of C. albicans from the peritoneal cavity to kidney. Taken together, this study reveals that unopsonized C. albicans evokes NADPH oxidase-independent NETosis through dectin-2 and its downstream signaling pathway and dectin-2-mediated NET helps restrain fungal dissemination.

Klíčová slova:

Candida albicans – Cell staining – Fluorescence imaging – Fluorescence microscopy – Histones – Intraperitoneal injections – Kidneys – Neutrophils


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Štítky
Hygiena a epidemiologie Infekční lékařství Laboratoř

Článek vyšel v časopise

PLOS Pathogens


2019 Číslo 11

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