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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Bibliographic Details
Authors: 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
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
Description
Summary: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.