A Novel Innate Response of Human Corneal Epithelium to Heat-killed Candida albicans by Producing Peptidoglycan Recognition Proteins

• Published in: PloS one 2015-06, Vol.10 (6), p.e0128039-e0128039
• Main Authors: Hua, Xia, Yuan, Xiaoyong, Li, Zhijie, Coursey, Terry G, Pflugfelder, Stephen C, Li, De-Quan
• Format: Article
• Language: English
• Subjects: Antifungal Agents - pharmacology; Bacteria; Candida albicans; Candida albicans - drug effects; Candida albicans - physiology; Carrier Proteins - metabolism; Causes of; Cells, Cultured; Cornea; Dendritic cells; Epithelial cells; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelial Cells - microbiology; Epithelium; Epithelium, Corneal - drug effects; Epithelium, Corneal - immunology; Epithelium, Corneal - microbiology; Fungal infections; Fungi; Gene expression; Genetic aspects; Hot Temperature; Human behavior; Humans; Immune response; Immune system; Immunity, Innate - drug effects; Infections; Inhibitors; Innate immunity; Insects; Keratitis; Lectins, C-Type - metabolism; Macrophages; Mammals; Medicine; Microorganisms; mRNA; NF-kappa B - metabolism; NF-κB protein; Nuclear transport; Pattern recognition; Peptidoglycan recognition proteins; Phagocytes; Phagocytosis; Physiological aspects; Prevention; Proteins; Receptors; Recognition; Recombinant Proteins - pharmacology; Rodents; Signal transduction; Signal Transduction - drug effects; Stem cells; Toll-like receptors; Translocation; Viral infections
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0128039

Fungal infections of the cornea can be sight-threatening and have a worse prognosis than other types of microbial corneal infections. Peptidoglycan recognition proteins (PGLYRP), which are expressed on the ocular surface, play an important role in the immune response against bacterial corneal infections by activating toll-like receptors (TLRs) or increasing phagocytosis. However, the role of PGLYRPs in innate immune response to fungal pathogens has not been investigated. In this study, we observed a significant induction of three PGLYRPs 2-4 in primary human corneal epithelial cells (HCECs) exposed to live or heat-killed Candida albicans (HKCA). The C-type lectin receptor dectin-1 plays a critical role in controlling Candida albicans infections by promoting phagocytic activity and cytokine production in macrophages and dendritic cells. Here, we demonstrate that dectin-1 is expressed by normal human corneal tissue and primary HCECs. HKCA exposure increased expression of dectin-1 on HCECs at mRNA and protein levels. Interestingly, dectin-1 neutralizing antibody, IκB-α inhibitor BAY11-7082, and NF-κB activation inhibitor quinazoline blocked NF-κB p65 nuclear translocation, as well as the induction of the PGLYRPs by HKCA in HCECs. Furthermore, rhPGLYRP-2 was found to suppress colony-forming units of Candida albicans in vitro. In conclusion, these findings demonstrate that dectin-1 is expressed by human corneal epithelial cells, and dectin-1/NF-κB signaling pathway plays an important role in regulating Candida albicans/HKCA-induced PGLYRP secretion by HCECs.