title: TLR9 and TLR7/8 activation induces formation of keratic precipitates and giant macrophages in the mouse cornea.
abstract: Macrophage adherence to the inner corneal surface and formation of MGCs in the stroma are common signs of chronic inflammation following corneal infection. To determine whether macrophage adherence (known clinically as KPs) and giant cell formation were specific to innate immune activation via particular TLR ligands, macrophage activation was examined in a murine model of TLR-mediated corneal inflammation. The corneal epithelium was debrided and highly purified TLR ligands were topically applied once to the cornea of TLR7(-/-), TLR9(-/-), Cx3cr1(gfp/+), CD11c(eYFP), and IL-4(-/-) mice. At 1 week post-treatment macrophage activation and phenotype was evaluated in the cornea. Treatment with TLR2, TLR3, TLR4, and TLR5 ligands caused an increase in the number of activated stromal macrophages in the central cornea at 1 week post-treatment. However, treatment with TLR9 ligand CpG-ODN and the TLR7/8 ligand R848/Resiquimod led to an accumulation of macrophages on the corneal endothelium and formation of multinucleated giant macrophages in the corneal stroma. We suggest that giant cell formation, which is a characteristic feature of granuloma formation in many tissues, may be a unique feature of TLR9- and TLR7/8-mediated macrophage activation.
authors.affiliation: *Department of Optometry and Vision Sciences, University of Melbourne, Victoria, Australia; Department of Anatomy and Developmental Biology, Monash University, Victoria, Australia; School of Molecular Sciences, Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Australia; Department of Ophthalmology, Institute of Medical Sciences, University of Aberdeen, United Kingdom; and Ocular Immunology Program, Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Australia holly.chinnery@unimelb.edu.au.
authors.forename: Holly R
authors.initials: HR
authors.lastname: Chinnery
authors.affiliation: *Department of Optometry and Vision Sciences, University of Melbourne, Victoria, Australia; Department of Anatomy and Developmental Biology, Monash University, Victoria, Australia; School of Molecular Sciences, Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Australia; Department of Ophthalmology, Institute of Medical Sciences, University of Aberdeen, United Kingdom; and Ocular Immunology Program, Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Australia.
authors.forename: Cheng Mee
authors.initials: CM
authors.lastname: Leong
authors.affiliation: *Department of Optometry and Vision Sciences, University of Melbourne, Victoria, Australia; Department of Anatomy and Developmental Biology, Monash University, Victoria, Australia; School of Molecular Sciences, Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Australia; Department of Ophthalmology, Institute of Medical Sciences, University of Aberdeen, United Kingdom; and Ocular Immunology Program, Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Australia.
authors.forename: Weisan
authors.initials: W
authors.lastname: Chen
authors.affiliation: *Department of Optometry and Vision Sciences, University of Melbourne, Victoria, Australia; Department of Anatomy and Developmental Biology, Monash University, Victoria, Australia; School of Molecular Sciences, Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Australia; Department of Ophthalmology, Institute of Medical Sciences, University of Aberdeen, United Kingdom; and Ocular Immunology Program, Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Australia.
authors.forename: John V
authors.initials: JV
authors.lastname: Forrester
authors.affiliation: *Department of Optometry and Vision Sciences, University of Melbourne, Victoria, Australia; Department of Anatomy and Developmental Biology, Monash University, Victoria, Australia; School of Molecular Sciences, Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Australia; Department of Ophthalmology, Institute of Medical Sciences, University of Aberdeen, United Kingdom; and Ocular Immunology Program, Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Australia.
authors.forename: Paul G
authors.initials: PG
authors.lastname: McMenamin
mesh_terms: D000818:Animals; D003315:Cornea / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D015726:Giant Cells / Q000276:immunology / Q000378:metabolism; D007634:Keratitis / Q000276:immunology* / Q000378:metabolism; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D051199:Toll-Like Receptor 7 / Q000276:immunology* / Q000378:metabolism; D051200:Toll-Like Receptor 8 / Q000276:immunology* / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000276:immunology* / Q000378:metabolism
chemical_list: D008562:Membrane Glycoproteins; C552579:TLR8 protein, mouse; C477038:Tlr7 protein, mouse; C495370:Tlr9 protein, mouse; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D051217:Toll-Like Receptor 9
keywords: Toll-like receptor; anterior uveitis; innate inflammation