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

Abstract

Vaginal candidiasis is an extremely common disease predominantly caused by four phylogenetically diverse species: Candida albicans, C. glabrata, C. parapsilosis, and C. tropicalis.Using a time course infection model of vaginal epithelial cells and dual RNA-Sequencing, we show that these species exhibit distinct pathogenicity patterns, 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 early stages of infections, which is characterized by sublethal mitochondrial signalling inducing a protective type I interferon response. At 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, characterized by protective mitochondriaassociated type I interferon signalling and a species-specific damage-driven response.

It Takes Two to Tango: How a Dysregulation of the Innate Immunity, Coupled With Candida Virulence, Triggers VVC Onset

“…Specifically, a biphasic host-response by vaginal epithelium has been observed. Such response is characterized by an early activation of mitochondria-induced type I IFN signaling which is shared by all the species considered ( C. albicans , C. glabrata , C. parapsilosis , and C. tropicalis ); the response becomes then species-specific only in the late stages of infection ( Pekmezovic et al, 2021 ). This review will focus on C. albicans induced VVC, particularly on the interactions occurring at the fungus-epithelium interface.…”

Recurrent Vulvovaginal Candidiasis: a Dynamic Interkingdom Biofilm Disease of Candida and Lactobacillus

“…This may be a contributing factor in the process by which L. crispatus is able to outcompete Candida during VVC and potentially re-establish a healthy microbiome. Furthermore, the pry1 gene, encoding a secreted glycoprotein associated with virulence and sterol binding in the presence of lactate, was found to be downregulated in dual-species biofilms ( 44 ). Thus, L. crispatus may possess a mechanism by which it can suppress lactate-associated virulence in C. albicans .…”

“…Thus, L. crispatus may possess a mechanism by which it can suppress lactate-associated virulence in C. albicans . Species-specific differential transcriptomic profiles in vaginal candidiasis have been demonstrated, and therefore, interactions between Lactobacillus and other prevalent Candida species should be considered ( 44 ). These data collectively show a potentially probiotic effect of L. crispatus against C. albicans in nonacidic environments.…”

Host lung environment limits Aspergillus fumigatus germination through a SskA-dependent signaling response

“…Recent work examining the inflammatory response of vaginal epithelial cells to Candida spp. demonstrate an early, homogeneous type I IFN response to all Candida spp., but at later time points, the inflammatory response diverges in a species specific and damage-dependent manner 62 .…”

“…Our study also identifies a role for the loss of SakA MAPK signaling in enhancing conidial germination, particularly in low glucose environments. This likely comes with the recompense of decreased resistance to osmotic and oxidative stress, which could be critical to disease progression during chronic fungal diseases 62 . Thus, future studies must address the role of these traits and pathways in both acute and chronic models of aspergillosis.…”