Hannah Brown Harding, Geneva N Kwaku, Christopher M Reardon, Nida S Khan, Daniel Zamith-Miranda, Robert Zarnowski, Jenny M Tam, Collins K Bohaen, Lauren Richey, Kenta Mosallanejad, Arianne J Crossen, Jennifer L Reedy, Rebecca A Ward, Diego A Vargas-Blanco, Kyle J Basham, Roby P Bhattacharyya, Jeniel E Nett, Michael K Mansour, Frank L van de Veerdonk, Vinod Kumar, Jonathan C Kagan, David R Andes, Joshua D Nosanchuk, Jatin M Vyas
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...
January 2, 2024: Nature Microbiology