Vaginal Clinical Isolates of <em>Candida albicans</em> Differentially Modulate Complosome Activation in Vaginal Epithelial Cells

In this in vitro study, we compared two clinical vaginal strains of C. albicans, a Colonizing strain from a healthy woman and a strain from a VVC patient, for their ability to activate the complosome and release anaphylatoxins in vaginal epithelial cells (VECs). The complosome controls different activities in innate immune cells and epithelial cells; however, its role in the response of VECs to Candida remains untested. Our results show that: i) both strains triggered 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 of both C5 and C5a in VECs, while no increase in C5a release was observed after infection with either strain; iii) Cathepsinfamily 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 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 to find new therapeutic targets against vaginal fungal infections.