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

English version

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
prolekare.web.journal.doi_sk: https://doi.org/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:

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

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