Normal Human Gingival Epithelial Cells SenseC. parapsilosisby Toll-Like Receptors and Module Its Pathogenesis through Antimicrobial Peptides and Proinflammatory Cytokines

Raouf Bahri,Sèverine Curt,Mahmoud Rouabhia,Dalila Saidane-Mosbahi

doi:10.1155/2010/940383

Raouf Bahri, Sèverine Curt + Show 2 more

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https://doi.org/10.1155/2010/940383

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Abstract

This study was designed to investigate the interaction between C. parapsilosis and human epithelial cells using monolayer cultures and an engineered human oral mucosa (EHOM). C. parapsilosis was able to adhere to gingival epithelial cells and to adopt the hyphal form in the presence of serum. Interestingly, when cultured onto the engineered human oral mucosa (EHOM), C. parapsilosis formed small biofilm and invaded the connective tissue. Following contact with C. parapsilosis, normal human gingival epithelial cells expressed high levels of Toll-like receptors (TLR)-2, -4, and -6, but not TLR-9 mRNA. The upregulation of TLRs was paralleled by an increase of IL-1β, TNFα, and IFNγ mRNA expression, suggesting the involvement of these cytokines in the defense against infection with C. parapsilosis. The active role of epithelial cells in the innate immunity against C. parapsilosis infection was enhanced by their capacity to express high levels of human beta-defensin-1, -2, and -3. The upregulation of proinflammatory cytokines and antimicrobial peptide expression may explain the growth inhibition of C. parapsilosis by the gingival epithelial cells. Overall results provide additional evidence of the involvement of epithelial cells in the innate immunity against C. parapsilosis infections.

Highlights

Fungal infections caused by Candida species are increasing, in immunocompromized individuals [1]
Given that C. parapsilosis can be acquired from different sites including soil and marine environments, and that C. parapsilosis is considered as an emerging pathogen in humans, we proposed to study (1) the virulence of C. parapsilosis when cultured under the appropriate conditions, and its susceptibility to an antifungal agent, (2) the ability of C. parapsilosis to attach to normal human epithelial cells in a monolayer culture and to form biofilm when used to infect engineered human oral mucosa (EHOM) in vitro, and (3) epithelial cell defenses against C. parapsilosis infection by investigating the gene activation of Toll-like receptors (TLR), antimicrobial peptides (HBD-1, -2, -3, and -4), and pro-inflammatory cytokines (IL-1β, TNFα, and IFNγ)
Following the extraction and identification of C. parapsilosis, we were concerned about its possible side effects on humans; we tested its susceptibility to an antifungal agent

Summary

Introduction

Fungal infections caused by Candida species are increasing, in immunocompromized individuals [1]. Infections by other Candida species are gaining ground worldwide, in nosocomial settings. These emerging candidiases involve various Candida species, including C. tropicalis, C. krusei, C. glabrata, and C. parapsilosis [2]. C. parapsilosis has been isolated from the oral cavity of of HIV-infected [7] and diabetic individuals [8]. These studies document C. parapsilosis pathogenicity, further investigations are warranted to determine how human tissues can interact with, and prevent C. parapsilosis infection

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