Candida albicans induces TLR2/MyD88/NF-κB signaling and inflammation in oral lichen planus-derived keratinocytes

  • Jianwei Liu Shandong University Affilicated Qilu Hospital, Jinan, Shandong, China
  • Fanghui Geng Huashan Hospital, Fudan University, Shanghai, China
  • Hongying Sun Huashan Hospital, Fudan University, Shanghai, China
  • Xiaxia Wang Huashan Hospital, Fudan University, Shanghai, China
  • Hui Zhang Huashan Hospital, Fudan University
  • Qiaozhen Yang Huashan Hospital, Fudan University, Shanghai, China
  • Jie Zhang Huashan Hospital, Fudan University, Shanghai, China
Keywords: Apoptosis, Candida albicans, keratinocyte, oral lichen planus, Toll-like receptor

Abstract

Introduction: The risk of oral lichen planus (OLP), a chronic inflammatory oral mucosal disease, becoming malignant increases by 21-fold in patients with fungal infection. This study examined the impact of Candida albicans exposure on Toll-like receptor (TLR) signaling in primary keratinocyte cultures obtained from OLP patients.

Methodology: Following co-culture of primary OLP keratinocyte cultures with C. albicans for 24 hours, inflammatory cytokine concentrations were determined by ELISA. TLR2, MyD88, and NF-κBp65 mRNA and protein expression were assessed using quantitative RT-PCR and Western blot analyses, respectively. Keratinocyte apoptosis was also determined by flow cytometry.

Results: IL-10, IL-8, IL-2, and TNF-ɑ levels were significantly higher following co-culture with C. albicans (all p ≤ 0.034). MyD88, NF-κB p65, and TLR2 mRNA (all p < 0.001) and protein (all p ≤ 0.004) expression levels were significantly higher in OLP keratinocytes following C. albicans exposure. Finally, the apoptosis rates of OLP keratinocytes were 21.2%, 29.4%, and 25.4% for the control cells and 3.9%, 5.6%, and 4.4% for those exposed to C. albicans, suggesting that co-culture with C. albicans inhibits the apoptosis of OLP keratinocytes.

Conclusions: C. albicans activates the TLR2/MyD88/NF-κB signaling pathway in OLP keratinocytes, resulting in increased cytokine expression and decreased keratinocyte apoptosis. Two key events in the pathogenesis of OLP and its progression to malignancy, namely increased inflammation and decreased apoptosis, were induced by exposure to C. albicans. Thus, targeting this signaling pathway may represent a novel therapeutic strategy to prevent OLP malignant transformation.

Author Biographies

Fanghui Geng, Huashan Hospital, Fudan University, Shanghai, China

Department of Stomatology

Hongying Sun, Huashan Hospital, Fudan University, Shanghai, China

Department of Stomatology

Xiaxia Wang, Huashan Hospital, Fudan University, Shanghai, China

Department of Stomatology

Hui Zhang, Huashan Hospital, Fudan University
Department of Stomatology
Qiaozhen Yang, Huashan Hospital, Fudan University, Shanghai, China

Department of Stomatology

Jie Zhang, Huashan Hospital, Fudan University, Shanghai, China

Department of Stomatology

Published
2018-09-30
How to Cite
1.
Liu J, Geng F, Sun H, Wang X, Zhang H, Yang Q, Zhang J (2018) Candida albicans induces TLR2/MyD88/NF-κB signaling and inflammation in oral lichen planus-derived keratinocytes. J Infect Dev Ctries 12:780-786. doi: https://doi.org/10.3855/jidc.8062
Section
Original Articles