title: A Novel Innate Response of Human Corneal Epithelium to Heat-killed Candida albicans by Producing Peptidoglycan Recognition Proteins.
abstract: 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.
authors.affiliation: Tianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, Clinical College of Ophthalmology, Tianjin Medical University, Tianjin, China; Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX, United States of America.
authors.forename: Xia
authors.initials: X
authors.lastname: Hua
authors.affiliation: Tianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, Clinical College of Ophthalmology, Tianjin Medical University, Tianjin, China; Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX, United States of America.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX, United States of America.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Li
authors.affiliation: Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX, United States of America.
authors.forename: Terry G
authors.initials: TG
authors.lastname: Coursey
authors.affiliation: Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX, United States of America.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Pflugfelder
authors.affiliation: Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX, United States of America.
authors.forename: De-Quan
authors.initials: DQ
authors.lastname: Li
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D019573:Epithelium, Corneal / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology*; D006358:Hot Temperature; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D037181:Lectins, C-Type / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D000099181:Dectin-1
chemical_list: D000935:Antifungal Agents; D002352:Carrier Proteins; D037181:Lectins, C-Type; D016328:NF-kappa B; D011994:Recombinant Proteins; D000099181:Dectin-1; C118897:peptidoglycan recognition protein