Nat Microbio: Candida infection triggers the protective immune response of vaginal epithelial cells and the mechanism of tissue repair

News from April 6, 2021 //---Vaginal candidiasis is an extremely common infectious disease, mainly caused by the following four pathogens: Candida albicans; Candida glabrata ( Candida glabrata, Candida parapsilosis; and Candida tropicalis.
In a recent study published in the journal Nature Microbiology, Professor Bernhard Hube from the University of Jena, Germany (Friedrich-Schiller-Universität Jena) and others used vaginal epithelial cell infection models and dual RNA sequencing methods to reveal these The unique pathogenic pattern exhibited by species, and proved that this difference is determined by the highly species-specific transcription profile during the infection process.
In contrast, host cells are uniform to all species in the early stages of infection, and are characterized by a protective type I IFN response induced by mitochondrial sublethal signaling.
In the later stage, the host's transcription map differs due to species differences at the time of infection.

(Image source: www.
nature.
com)

First, in order to study the infectivity of the above four common pathogens to vaginal epithelial cells, the author first compared their adhesion, invasiveness, and damage to host cells and other phenotypic characteristics.
The results showed that although the adhesion rates of all pathogens were similar, only C.
albicans transformed into hyphae, which infected cells and caused necrotic damage.
In contrast, C.
glabrata and C.
tropicalis do not infect host cells and cause relatively low damage.
C.
parapsilosis maintained its yeast form throughout the process, and did not cause any infection or host cell damage.
The above results indicate that different species will exhibit completely different phenotypic characteristics, infectivity and ability to damage host cells when facing host cells.

(Figure 1, Establishment of in vitro infection model of Candida and pathological analysis)

Further, the author analyzed the gene expression of different pathogens during infection.
The results showed that after 3 hours of infection, the carbohydrate metabolism and stress response signals in C.
albicans and C.
glabrata were significantly enhanced, and the adhesion transport, ribosome assembly and translation-related gene expression in C.
parapsilosis were significantly increased, and C.
The up-regulated genes in tropicalis are mainly RNA processing, ribosome synthesis and ergosterol synthesis.
In the later stage of infection, the gene expression of different pathogens showed an obvious trend of "functional confluence".

(Figure 2, the dynamic trend of its own transcriptomics during Candida infection of the host)

Different from pathogens, host cells show similar characteristics of gene expression changes when they are infected from the outside, the most representative of which is the activation of type I interferon signals and mitochondrial function-related signals.
In recent years, the mitochondria in host cells have been considered as the center of natural immune signals, and they also have the effect of activating type I IFN.
The results of the study show that the host will activate ISG and other related genes after pathogen infection, but this phenomenon does not depend on the existence of the virus.
On this basis, the author specifically blocked the IFN signal in the host cell.
This treatment severely affected the tolerance of the host cell to pathogen infection.
Taken together, these results indicate that type I IFN signaling plays a key role in host cells' resistance to Candida infection.
(Bioon.
com)

Original source: Pekmezovic, M.
, Hovhannisyan, H.
, Gresnigt, MS et al.
Candida pathogens induce protective mitochondria-associated type I interferon signalling and a damage-driven response in vaginal epithelial cells .
Nat Microbiol (2021).
https:/ /doi.
org/10.
1038/s41564-021-00875-2