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 Kumar; Jonathan C. Kagan; David R. Andes; Joshua D. Nosanchuk; Jatin M. Vyas

doi:10.1038/s41564-023-01546-0

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

Medicine

Research output: Contribution to journal › Article › peer-review

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 language	English (US)
Pages (from-to)	95-107
Number of pages	13
Journal	Nature Microbiology
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41564-023-01546-0
State	Published - Jan 2024

ASJC Scopus subject areas

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

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Brown Harding, H., Kwaku, G. N., Reardon, C. M., Khan, N. S., Zamith-Miranda, D., Zarnowski, R., Tam, J. M., Bohaen, C. K., Richey, L., Mosallanejad, K., Crossen, A. J., Reedy, J. L., Ward, R. A., Vargas-Blanco, D. A., Basham, K. J., Bhattacharyya, R. P., Nett, J. E., Mansour, M. K., van de Veerdonk, F. L., ... Vyas, J. M. (2024). Candida albicans extracellular vesicles trigger type I IFN signalling via cGAS and STING. Nature Microbiology, 9(1), 95-107. https://doi.org/10.1038/s41564-023-01546-0

Brown Harding, H, Kwaku, GN, Reardon, CM, Khan, NS, Zamith-Miranda, D, Zarnowski, R, Tam, JM, Bohaen, CK, Richey, L, Mosallanejad, K, Crossen, AJ, Reedy, JL, Ward, RA, Vargas-Blanco, DA, Basham, KJ, Bhattacharyya, RP, Nett, JE, Mansour, MK, van de Veerdonk, FL, Kumar, V, Kagan, JC, Andes, DR, Nosanchuk, JD & Vyas, JM 2024, 'Candida albicans extracellular vesicles trigger type I IFN signalling via cGAS and STING', Nature Microbiology, vol. 9, no. 1, pp. 95-107. https://doi.org/10.1038/s41564-023-01546-0

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title = "Candida albicans extracellular vesicles trigger type I IFN signalling via cGAS and STING",

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.",

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doi = "10.1038/s41564-023-01546-0",

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AU - Brown Harding, Hannah

AU - Kwaku, Geneva N.

AU - Reardon, Christopher M.

AU - Khan, Nida S.

AU - Zamith-Miranda, Daniel

AU - Zarnowski, Robert

AU - Tam, Jenny M.

AU - Bohaen, Collins K.

AU - Richey, Lauren

AU - Mosallanejad, Kenta

AU - Crossen, Arianne J.

AU - Reedy, Jennifer L.

AU - Ward, Rebecca A.

AU - Vargas-Blanco, Diego A.

AU - Basham, Kyle J.

AU - Bhattacharyya, Roby P.

AU - Nett, Jeniel E.

AU - Mansour, Michael K.

AU - van de Veerdonk, Frank L.

AU - Kumar, Vinod

AU - Kagan, Jonathan C.

AU - Andes, David R.

AU - Nosanchuk, Joshua D.

AU - Vyas, Jatin M.

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N2 - 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.

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

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