Staphylococcus aureus lipoproteins trigger human corneal epithelial innate response through toll-like receptor-2.
Bacterial lipoproteins (LP) are a family of cell wall components found in a wide variety of bacteria. In this study, we characterized the response of HUCL, a telomerase-immortalized human corneal epithelial cell (HCEC) line, to LP isolated from Staphylococcus (S) aureus. S. aureus LP (saLP) prepared by Triton X-114 extraction stimulated the activation of NF-kappaB, JNK, and P38 signaling pathways in HUCL cells. The extracts failed to stimulate NF-kappaB activation in HUCL cells after lipoprotein lipase treatment and in cell lines expressing TLR4 or TLR9, but not TLR2, indicating lipoprotein nature of the extracts. saLP induced the up-regulation of a variety of inflammatory cytokines and chemokines (IL-6, IL-8, ICAM-1), antimicrobial molecules (hBD-2, LL-37, and iNOS), and homeostasis genes (Mn-SOD) at both the mRNA level and protein level. Similar inflammatory response to saLP was also observed in primarily cultured HCECs using the production of IL-6 as readout. Moreover, TLR2 neutralizing antibody blocked the saLP-induced secretion of IL-6, IL-8 and hBD2 in HUCL cells. Our findings suggest that saLP activates TLR2 and triggers innate immune response in the cornea to S. aureus infection via production of proinflammatory cytokines and defense molecules.
Li
Qiong
Q
Kresge Eye Institute/Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Kumar
Ashok
A
Gui
Jian-Fang
JF
Yu
Fu-Shin X
FS
D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D001426:Bacterial Proteins / Q000276:immunology*; D002460:Cell Line; D003315:Cornea / Q000276:immunology* / Q000382:microbiology*; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000382:microbiology; D006801:Humans; D008074:Lipoproteins / Q000276:immunology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology*; D013482:Superoxide Dismutase / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D016207:Cytokines; D008074:Lipoproteins; D016328:NF-kappa B; D051195:Toll-Like Receptor 2; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4