Candida albicans extracellular vesicles trigger type I IFN signalling via cGAS and STING

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 KumarJonathan C. Kagan, David R. Andes, Joshua D. Nosanchuk, Jatin M. Vyas

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)95-107
Number of pages13
JournalNature Microbiology
Volume9
Issue number1
DOIs
StatePublished - Jan 2024

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Applied Microbiology and Biotechnology
  • Genetics
  • Microbiology (medical)
  • Cell Biology

Fingerprint

Dive into the research topics of 'Candida albicans extracellular vesicles trigger type I IFN signalling via cGAS and STING'. Together they form a unique fingerprint.

Cite this