Candida albicans-Cell Interactions Activate Innate Immune Defense in Human Palate Epithelial Primary Cells via Nitric Oxide (NO) and β-Defensin 2 (hBD-2)

Abstract

The presence of Candida albicans in the biofilm underlying the dental prosthesis is related to denture stomatitis (DS), an inflammatory reaction of the oral mucosa. The oral epithelium, a component of the innate immune response, has the ability to react to fungal invasion. In this study, we evaluated the in vitro effect of viable C. albicans on the apoptosis, nitric oxide (NO) production, and β-defensin 2 (hBD-2) expression and production of human palate epithelial cells (HPECs). We further determined whether or not these effects were correlated with fungal invasion of epithelial cells. Interaction between HPEC primary culture and C. albicans was obtained through either direct or indirect cell–cell contact with a supernatant from a hyphal fungus. We found that the hyphae supernatants were sufficient to induce slight HPEC apoptosis, which occurred prior to the activation of the specific mechanisms of epithelial defense. The epithelial defense responses were found to occur via NO and antimicrobial peptide hBD-2 production only during direct contact between C. albicans and HPECs and coincided with the fungus’s intraepithelial invasion. However, although the hBD-2 levels remained constant in the HPEC supernatants over time, the NO release and hBD-2 gene expression were reduced at a later time (10 h), indicating that the epithelial defense capacity against the fungal invasion was not maintained in later phases. This aspect of the immune response was associated with increased epithelial invasion and apoptosis maintenance.

Antifungal activity of Punicalagin–nystatin combinations against Candida albicans

“…All experimental procedures were approved by the Committee for Ethics in Research on Human Beings of Bauru School of Dentistry, University of São Paulo (CAAE, 44951715.6.0000.5417). HPEC were cultured as previously described by Klingbeil, Mathor, Giudice, Yoshito, and Dos Santos Pinto (2012) (Casaroto et al., 2019; Klingbeil et al., 2012). HGF were cultured in Dulbecco's Modified Eagles Medium (DMEM; Gibco Invitrogen) containing 10% fetal bovine serum (FBS; Gibco Invitrogen) and penicillin/streptomycin (100 IU/ml/100 μg/ml; Gibco Invitrogen).…”

The impact of the Fungus-Host-Microbiota interplay uponCandida albicansinfections: current knowledge and new perspectives

“…In the oral epithelium, nitric oxide and human-β-defensin (hBD)-2 production contribute to the early defensive response following direct contact with C. albicans and intra-epithelial invasion (Casaroto et al . 2019 ). In the GI tract, mucins produced by goblet cells suppress the yeast-hypha transition, surface adhesion and biofilm formation of C. albicans , thereby minimizing the capacity of the fungus to attach to, invade, and damage the epithelium (Kavanaugh et al .…”

Candidalysin Is a Potent Trigger of Alarmin and Antimicrobial Peptide Release in Epithelial Cells

“…A number of host protective AMPs and alarmins are induced in response to C. albicans infection within a variety of cell types, including human palate [33], vaginal [29] and oesophageal [32] epithelium, as well as human keratinocytes [44], blood-derived neutrophils [45] and the intestinal cell line Caco2 [34]. However, the identity of the specific fungal factors that trigger these alarmins and AMPs is largely unknown.…”

“…AMPs on the other hand, largely function to damage cell walls resulting in pathogen lysis, in addition to their immune-modulating abilities [28]. S100 proteins [29][30][31] and defensins [31][32][33][34] are highlighted as two main alarmin and AMP molecules induced by C. albicans, functioning to recruit neutrophils [29,30] and permeabilise fungal cell walls [35], respectively. However, information on the specific C. albicans factors that trigger the secretion of these molecules, or indeed other alarmins and AMPs, has largely remained elusive.…”