Candida pathogens induce protective mitochondria-associated type I interferon signalling and a damage-driven response in vaginal epithelial cells

Pekmezovic, Marina; Hovhannisyan, Hrant, 1992-; Gresnigt, Mark S.; Iracane, Elise; Oliveira Pacheco, João; Siscar Lewin, Sofía; Seemann, Eric; Qualmann, Britta; Kalkreuter, Till; Müller, Sylvia; Kamradt, Thomas; Mogavero, Selene; Brunke, Sascha; Butler, Geraldine; Gabaldón Estevan, Juan Antonio, 1973-; Hube, Bernhard

Candida pathogens induce protective mitochondria-associated type I interferon signalling and a damage-driven response in vaginal epithelial cells

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dc.contributor.author Pekmezovic, Marina
dc.contributor.author Hovhannisyan, Hrant, 1992-
dc.contributor.author Gresnigt, Mark S.
dc.contributor.author Iracane, Elise
dc.contributor.author Oliveira Pacheco, João
dc.contributor.author Siscar Lewin, Sofía
dc.contributor.author Seemann, Eric
dc.contributor.author Qualmann, Britta
dc.contributor.author Kalkreuter, Till
dc.contributor.author Müller, Sylvia
dc.contributor.author Kamradt, Thomas
dc.contributor.author Mogavero, Selene
dc.contributor.author Brunke, Sascha
dc.contributor.author Butler, Geraldine
dc.contributor.author Gabaldón Estevan, Juan Antonio, 1973-
dc.contributor.author Hube, Bernhard
dc.date.accessioned 2021-07-15T06:26:50Z
dc.date.issued 2021
dc.description.abstract 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.
dc.description.sponsorship M.P., H.H., E.I., J.O.P., T.G., G.B. and B.H. received funding from the European Union Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant no. 642095 (OPATHY). B.H. also received support from the German Research Foundation within the Collaborative Research Centre/Transregio 124 FungiNet (project C1). M.S.G. was supported by the German Research Foundation Emmy Noether Programme (project no. 434385622/GR 5617/1-1). We acknowledge the support of the Spanish Ministry of Science, Innovation and Universities (grant no. PGC2018-099921-B-I00) to the European Molecular Biology Laboratory partnership, the Centro de Excelencia Severo Ochoa and the CERCA Programme/Generalitat de Catalunya. We thank C. Kämnitz from the Electron Microscopy Center in Jena for the sample preparation for TEM. The schematic models in Figs. 4–6 were created with images adapted from Servier Medical Art (Servier).
dc.format.mimetype application/pdf
dc.identifier.citation Pekmezovic M, Hovhannisyan H, Gresnigt MS, 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. Candida pathogens induce protective mitochondria-associated type I interferon signalling and a damage-driven response in vaginal epithelial cells. Nat Microbiol. 2021;6(5):643-57. DOI: 10.1038/s41564-021-00875-2
dc.identifier.doi http://dx.doi.org/10.1038/s41564-021-00875-2
dc.identifier.issn 2058-5276
dc.identifier.uri http://hdl.handle.net/10230/48185
dc.language.iso eng
dc.publisher Nature Research
dc.relation.ispartof Nat Microbiol. 2021;6(5):643-57
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/642095
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PGC2018-099921-B-I00
dc.rights © Springer Nature Publishing AG Pekmezovic M, Hovhannisyan H, Gresnigt MS, 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. Candida pathogens induce protective mitochondria-associated type I interferon signalling and a damage-driven response in vaginal epithelial cells. Nat Microbiol. 2021;6(5):643-57. DOI: 10.1038/s41564-021-00875-2 [http://dx.doi.org/10.1038/s41564-021-00875-2]
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.subject.keyword Fungal host response
dc.subject.keyword Fungal pathogenesis
dc.subject.keyword Innate immunity
dc.subject.keyword Transcriptomics
dc.title Candida pathogens induce protective mitochondria-associated type I interferon signalling and a damage-driven response in vaginal epithelial cells
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/acceptedVersion

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Articles (Center for Genomic Regulation (CRG))
Articles (Departament de Medicina i Ciències de la Vida)
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