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...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
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| Format: | Article |
| Status: | Accepted version |
| Publication date: | 2021 |
| Country: | España |
| Institution: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repository: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:10230/48185 |
| Online Access: | http://hdl.handle.net/10230/48185 http://dx.doi.org/10.1038/s41564-021-00875-2 |
| Access Level: | Open access |
| Keyword: | Fungal host response Fungal pathogenesis Innate immunity Transcriptomics |
| _version_ | 1878733019391459328 |
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| author | Pekmezovic, Marina |
| 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 |
| author_browse | Brunke, Sascha Butler, Geraldine Gabaldón Estevan, Juan Antonio, 1973- Gresnigt, Mark S. Hovhannisyan, Hrant, 1992- Hube, Bernhard Iracane, Elise Kalkreuter, Till Kamradt, Thomas Mogavero, Selene Müller, Sylvia Oliveira Pacheco, João Pekmezovic, Marina Qualmann, Britta Seemann, Eric Siscar Lewin, Sofía |
| 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 |
| collection | Recercat. Dipósit de la Recerca de Catalunya |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_4e759e5dca4f2a77a58b9f7bd65bf392 |
| institution | 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) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:recercat.cat:10230/48185 |
| publishDate | 2021 |
| publishDateSort | 2021 |
| publisher | Nature Research |
| publisherStr | Nature Research |
| reponame_str | Recercat. Dipósit de la Recerca de Catalunya |
| spelling | 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 Fungal host response Fungal pathogenesis Innate immunity Transcriptomics 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. 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 Research http://hdl.handle.net/10230/48185 http://dx.doi.org/10.1038/s41564-021-00875-2 |
| 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 |
| status_str | acceptedVersion |
| title | 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_short | 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 |
| topic | Fungal host response Fungal pathogenesis Innate immunity Transcriptomics |
| topic_facet | Fungal host response Fungal pathogenesis Innate immunity Transcriptomics |
| url | http://hdl.handle.net/10230/48185 http://dx.doi.org/10.1038/s41564-021-00875-2 |