Nature microbiology · 2024
Candida albicans extracellular vesicles trigger type I IFN signalling via cGAS and STING.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
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Brown Harding Hannah, Kwaku Geneva N, Reardon Christopher M, Khan Nida S, Zamith-Miranda Daniel, Zarnowski Robert, Tam Jenny M, Bohaen Collins K, Richey Lauren, Mosallanejad Kenta, Crossen Arianne J, Reedy Jennifer L, Ward Rebecca A, Vargas-Blanco Diego A, Basham Kyle J, Bhattacharyya Roby P, Nett Jeniel E, Mansour Michael K, van de Veerdonk Frank L, Kumar Vinod, Kagan Jonathan C, Andes David R, Nosanchuk Joshua D, Vyas Jatin M
Аннотация
The host type I interferon (IFN) pathway is a major signature of inflammation induced by the human fungal pathogen, Candida albicans. However, the molecular mechanism for activating this pathway in the host defence against C. albicans remains unknown. Here we reveal that mice lacking cyclic GMP-AMP synthase (cGAS)-stimulator of IFN genes (STING) pathway components had improved survival following an intravenous challenge by C. albicans. Biofilm-associated C. albicans DNA packaged in extracellular vesicles triggers the cGAS-STING pathway as determined by induction of interferon-stimulated genes, IFNβ production, and phosphorylation of IFN regulatory factor 3 and TANK-binding kinase 1. Extracellular vesicle-induced activation of type I IFNs was independent of the Dectin-1/Card9 pathway and did not require toll-like receptor 9. Single nucleotide polymorphisms in cGAS and STING potently altered inflammatory cytokine production in human monocytes challenged by C. albicans. These studies provide insights into the early innate immune response induced by a clinically significant fungal pathogen.