title: Aspergillus fumigatus triggers innate immune response via NOD1 signaling in human corneal epithelial cells.
abstract: Fungal keratitis is a serious vision-threatening disease caused by fungi after corneal epithelium damage. We have previously shown a role of cell surface TLRs in Aspergillus fumigatus (A. fumigatus) keratitis. In the present study we showed that Human telomerase-immortalized corneal epithelial cells (HCECs) exposed to A. fumigatus elicited an inflammatory response consisting in increased interleukin-6 (IL-6), IL-8 and tumor necrosis factor (TNF)-α expression and innate defense molecules hBD2 and LL37 in a time-dependent manner. In this study we further investigated the role of intracellular nucleotide-binding oligomerization domain-containing protein (NOD)-like receptors, NOD1 in innate immune and inflammatory response to A. fumigatus. We showed that NOD1 and its downstream signaling molecules RIP2 and NF-κB p65 are expressed in HCECs challenged with either NOD1 specific ligand iE-DAP or A. fumigatus. More importantly, NOD1 knockdown attenuated A. fumigatus-triggered the expression of NOD1, and downstream signaling effectors RIP2 and NF-κB p65, as well as the secretion of IL-6, IL-8 and TNF-α, and the production of hBD2 and LL37. In conclusion, our results demonstrated that NOD1 is a prominent factor of innate immune and inflammatory response in HCECs against A. fumigatus, suggesting that NOD1 might be a potential novel therapeutic target for the treatment of fungal keratitis.
authors.affiliation: Department of Ophthalmology, Qilu Hospital of Shandong University, Wenhua Xi Road 107, Jinan, Shandong Province, 250012, PR China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Qilu Hospital of Shandong University, Wenhua Xi Road 107, Jinan, Shandong Province, 250012, PR China.
authors.forename: Jiayin
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Ophthalmology, Qilu Hospital of Shandong University, Wenhua Xi Road 107, Jinan, Shandong Province, 250012, PR China.
authors.forename: Zhaoting
authors.initials: Z
authors.lastname: Xin
authors.affiliation: Department of Ophthalmology, Qilu Hospital of Shandong University, Wenhua Xi Road 107, Jinan, Shandong Province, 250012, PR China. Electronic address: xywu8868@163.com.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Wu
mesh_terms: D023181:Antimicrobial Cationic Peptides; D001232:Aspergillus fumigatus / Q000502:physiology*; D015153:Blotting, Western; D054804:Cathelicidins / Q000378:metabolism; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D019573:Epithelium, Corneal / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D007378:Interleukins / Q000378:metabolism; D053474:Nod1 Signaling Adaptor Protein / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D013997:Time Factors; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D023083:beta-Defensins / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; C106641:DEFB4A protein, human; D007378:Interleukins; C119067:NOD1 protein, human; D053474:Nod1 Signaling Adaptor Protein; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D023083:beta-Defensins
keywords: Aspergillus fumigatus; HCECs; NOD1; inflammatory cytokine; innate immune