Candida pathogens induce protective mitochondria-associated type I interferon signalling and a damage-driven response in vaginal epithelial cells
Open accessAbstract
Vaginal candidiasis is an extremely common disease predominantly caused by four phylogenetically diverse species: Candida albicans; Candida glabrata; Candida parapsilosis; and Candida tropicalis. Using a time course infection model of vaginal epithelial cells and dual RNA sequencing, we show that these species exhibit distinct pathogenicity patterns, which are defined by highly species-specific transcriptional profiles during infection of vaginal epithelial cells. In contrast, host cells exhibit a homogeneous response to all species at the early stages of infection, which is characterized by sublethal mitochondrial signalling inducing a protective type I interferon response. At the later stages, the transcriptional response of the host diverges in a species-dependent manner. This divergence is primarily driven by the extent of epithelial damage elicited by species-specific mechanisms, such as secretion of the toxin candidalysin by C. albicans. Our results uncover a dynamic, biphasic response of vaginal epithelial cells to Candida species, which is characterized by protective mitochondria-associated type I interferon signalling and a species-specific damage-driven response.
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Host cell mitochondrial DNA release at early hours pi promotes a TII response in vaginal epithelial cell lines infected with Candida species.
“host cell mitochondrial DNA release at early hours pi promotes a TII response in vaginal epithelial cell lines infected with Candida species (30).”
From Overlooked <i>Candida glabrata</i> petites are echinocandin tolerant, induce host inflammatory responses, and display poor <i>in vivo</i> fitness (2023) · cites this paper as [30]
The TII response is also induced by bacterial, parasitic, and fungal infections.
“this response is also induced by bacterial, parasitic (43), and fungal infections (30, 44 – 48).”
From Overlooked <i>Candida glabrata</i> petites are echinocandin tolerant, induce host inflammatory responses, and display poor <i>in vivo</i> fitness (2023) · cites this paper as [30]
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Arastehfar, A., Daneshnia, F., Hovhannisyan, H., Fuentes, D., Cabrera, N., Quinteros, C., Ilkit, M., Ünal, N., Hilmioğlu-Polat, S., Jabeen, K., et al. (2023) · mBio · doi:10.1128/mbio.01180-23 · Cited by 27 · see citing works
“RNA was extracted using a previously described method (30), followed by DNase treatment (QIAGEN) and repurification of RNA samples using the QIAGEN RNeasy Kit.”
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Type I interferons during host–fungus interactions: Is antifungal immunity going viral?
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Self-citation
- Authors
- Pekmezovic, M., Hovhannisyan, H., Gresnigt, M. S., Iracane, E., Oliveira-Pacheco, J., Siscar-Lewin, S., Seemann, E., Qualmann, B., Kalkreuter, T., Müller, S., Kamradt, T., Mogavero, S., Brunke, S., Butler, G., Gabaldón, T., & Hube, B.
- Affiliations
- Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) (DE)
- Universitat Pompeu Fabra (ES)
- University College Dublin (IE)
- Jena University Hospital (DE)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Corresponding author
- Gabaldón, Toni
- Hube, Bernhard
- ORCID
- Venue
- Nature Microbiology
- Published
- 2021-03-22
- Volume
- 6
- Issue
- 5
- Pages
- 643-657
- ISSN
- 2058-5276 (ISSN-L)
- OpenAlex
- W3138689869
- Cited by
- 96
- References
- 104
- Citations by year
- 2026: 17 · 2025: 15 · 2024: 22 · 2023: 11 · 2022: 15 · 2021: 16
- FWCI
- 5.08
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Nature Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion)
- UPCommons institutional repository (Universitat Politècnica de Catalunya) (submittedVersion, public-domain)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Microbiology › Reproductive tract infections research
- Keywords
- vaginal candidiasis, Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis, vaginal epithelial cells, type I interferon signaling, mitochondrial signalling, candidalysin, epithelial damage, host-pathogen interaction, host transcriptional response
- MeSH terms
- Candida, Candidiasis, Vulvovaginal, Epithelial Cells, Female, Fungal Proteins, Humans, Interferon Type I, Mitochondria, Species Specificity, Vagina, Virulence
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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