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Nat Microbiol ; 6(5): 643-657, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33753919

RESUMO

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.


Assuntos
Candida/genética , Candidíase Vulvovaginal/microbiologia , Células Epiteliais/imunologia , Interferon Tipo I/imunologia , Mitocôndrias/imunologia , Candida/imunologia , Candida/isolamento & purificação , Candida/patogenicidade , Candidíase Vulvovaginal/genética , Candidíase Vulvovaginal/imunologia , Células Epiteliais/microbiologia , Feminino , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Humanos , Interferon Tipo I/genética , Mitocôndrias/genética , Especificidade da Espécie , Vagina/imunologia , Vagina/microbiologia , Virulência
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