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

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 th...

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Autores: 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
Tipo de documento: artigo
Estado:Versión aceptada para publicación
Data de publicação:2021
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/48185
Acesso em linha:http://hdl.handle.net/10230/48185
http://dx.doi.org/10.1038/s41564-021-00875-2
Access Level:Acceso aberto
Palavra-chave:Fungal host response
Fungal pathogenesis
Innate immunity
Transcriptomics
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spelling Candida pathogens induce protective mitochondria-associated type I interferon signalling and a damage-driven response in vaginal epithelial cellsPekmezovic, MarinaHovhannisyan, Hrant, 1992-Gresnigt, Mark S.Iracane, EliseOliveira Pacheco, JoãoSiscar Lewin, SofíaSeemann, EricQualmann, BrittaKalkreuter, TillMüller, SylviaKamradt, ThomasMogavero, SeleneBrunke, SaschaButler, GeraldineGabaldón Estevan, Juan Antonio, 1973-Hube, BernhardFungal host responseFungal pathogenesisInnate immunityTranscriptomicsVaginal 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.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).Nature Research20212021info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/48185http://dx.doi.org/10.1038/s41564-021-00875-2reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésNat Microbiol. 2021;6(5):643-57info:eu-repo/grantAgreement/EC/H2020/642095info:eu-repo/grantAgreement/ES/2PE/PGC2018-099921-B-I00© 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]info:eu-repo/semantics/openAccessoai:recercat.cat:10230/481852026-05-29T05:05:01Z
dc.title.none.fl_str_mv Candida pathogens induce protective mitochondria-associated type I interferon signalling and a damage-driven response in vaginal epithelial cells
title Candida pathogens induce protective mitochondria-associated type I interferon signalling and a damage-driven response in vaginal epithelial cells
spellingShingle Candida pathogens induce protective mitochondria-associated type I interferon signalling and a damage-driven response in vaginal epithelial cells
Pekmezovic, Marina
Fungal host response
Fungal pathogenesis
Innate immunity
Transcriptomics
title_short Candida pathogens induce protective mitochondria-associated type I interferon signalling and a damage-driven response in vaginal epithelial cells
title_full Candida pathogens induce protective mitochondria-associated type I interferon signalling and a damage-driven response in vaginal epithelial cells
title_fullStr Candida pathogens induce protective mitochondria-associated type I interferon signalling and a damage-driven response in vaginal epithelial cells
title_full_unstemmed Candida pathogens induce protective mitochondria-associated type I interferon signalling and a damage-driven response in vaginal epithelial cells
title_sort Candida pathogens induce protective mitochondria-associated type I interferon signalling and a damage-driven response in vaginal epithelial cells
dc.creator.none.fl_str_mv 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
author Pekmezovic, Marina
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Fungal host response
Fungal pathogenesis
Innate immunity
Transcriptomics
topic Fungal host response
Fungal pathogenesis
Innate immunity
Transcriptomics
description 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.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/48185
http://dx.doi.org/10.1038/s41564-021-00875-2
url http://hdl.handle.net/10230/48185
http://dx.doi.org/10.1038/s41564-021-00875-2
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Nat Microbiol. 2021;6(5):643-57
info:eu-repo/grantAgreement/EC/H2020/642095
info:eu-repo/grantAgreement/ES/2PE/PGC2018-099921-B-I00
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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