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

Autor: Pekmezovic M; Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Jena, Germany., Hovhannisyan H; Bioinformatics and Genomics Programme, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain.; Universitat Pompeu Fabra, Barcelona, Spain.; Life Sciences Department, Barcelona Supercomputing Center, Barcelona, Spain.; Mechanisms of Disease Department, Institute for Research in Biomedicine, Barcelona, Spain., Gresnigt MS; Junior Research Group Adaptive Pathogenicity Strategies, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Jena, Germany., Iracane E; School of Biomedical and Biomolecular Science and UCD Conway Institute of Biomolecular and Biomedical Research, Conway Institute, University College Dublin, Dublin, Ireland., Oliveira-Pacheco J; School of Biomedical and Biomolecular Science and UCD Conway Institute of Biomolecular and Biomedical Research, Conway Institute, University College Dublin, Dublin, Ireland., Siscar-Lewin S; Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Jena, Germany., Seemann E; Institute for Biochemistry I, Jena University Hospital-Friedrich Schiller University, Jena, Germany., Qualmann B; Institute for Biochemistry I, Jena University Hospital-Friedrich Schiller University, Jena, Germany., Kalkreuter T; Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Jena, Germany., Müller S; Institute of Immunology, Universitätsklinikum Jena, Jena, Germany., Kamradt T; Institute of Immunology, Universitätsklinikum Jena, Jena, Germany., Mogavero S; Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Jena, Germany., Brunke S; Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Jena, Germany., Butler G; School of Biomedical and Biomolecular Science and UCD Conway Institute of Biomolecular and Biomedical Research, Conway Institute, University College Dublin, Dublin, Ireland., Gabaldón T; Bioinformatics and Genomics Programme, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain. toni.gabaldon.bcn@gmail.com.; Universitat Pompeu Fabra, Barcelona, Spain. toni.gabaldon.bcn@gmail.com.; Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain. toni.gabaldon.bcn@gmail.com.; Life Sciences Department, Barcelona Supercomputing Center, Barcelona, Spain. toni.gabaldon.bcn@gmail.com.; Mechanisms of Disease Department, Institute for Research in Biomedicine, Barcelona, Spain. toni.gabaldon.bcn@gmail.com., Hube B; Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Jena, Germany. bernhard.hube@leibniz-hki.de.; Institute of Microbiology, Friedrich Schiller University, Jena, Germany. bernhard.hube@leibniz-hki.de.
Jazyk: angličtina
Zdroj: Nature microbiology [Nat Microbiol] 2021 May; Vol. 6 (5), pp. 643-657. Date of Electronic Publication: 2021 Mar 22.
DOI: 10.1038/s41564-021-00875-2
Abstrakt: 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.
Databáze: MEDLINE
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