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:Versión aceptada para publicación
Publication Date:2021
Country:España
Institution:Universitat Pompeu Fabra
Repository:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu: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.

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