Vaginal Clinical Isolates of Candida albicans Differentially Modulate Complosome Activation in Vaginal Epithelial Cells

TL;DR

This study shows that different strains of Candida albicans affect immune responses in vaginal cells differently, with one strain evading immune detection.

Contribution

The study reveals a novel immune evasion strategy by a Candida albicans strain through modulation of complosome activity in vaginal epithelial cells.

Findings

Colonizing C. albicans strain increases C3a release while VVC strain reduces C5 and C5a in vaginal epithelial cells.

VVC strain reduces cathepsin D activity and C5aR1 levels, suggesting immune evasion.

Colonizing strain increases intracellular C5aR1 without affecting C3aR levels.

Abstract

The complosome controls different activities in innate immune cells and epithelial cells; however, its role in the response of VECs to Candida remains untested. In this in vitro study, we compared two clinical vaginal strains of C. albicans, namely, a Colonizing strain from a healthy woman and a strain from a patient with vulvovaginal candidiasis (VVC), for their ability to activate the complosome and release anaphylatoxins in vaginal epithelial cells (VECs). Our results show the following: (i) both strains triggered the cleavage of C3 into C3a and C3b within VECs, while infection with the Colonizing strain led to greater release of the anaphylatoxin C3a; (ii) infection with the VVC isolate led to a strong reduction in both C5 and C5a in VECs, while no increase in C5a release was observed after infection with either strain; (iii) cathepsin-family gene expression and cathepsin D activity were reduced in VECs infected with the VVC strain but not in those infected with the Colonizing strain; (iv) infection with the Colonizing strain induced a significant increase in intracellular C5aR1 while intracellular C3aR levels remained unchanged. Collectively, our data suggests the propensity of this VVC strain to inactivate the C5/C5aR1 axis and to reduce the C3/C3aR axis, dampening the activity of the complosome in VECs. These effects exerted by the VVC strain suggest a novel strategy of immune evasion by C. albicans and may open new perspectives for finding new therapeutic targets against vaginal fungal infections.

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