TLR9 and TLR7/8 activation induces formation of keratic precipitates and giant macrophages in the mouse cornea. Issue 1 (21st November 2014)

• Record Type: Journal Article
• Authors: Chinnery, Holly R; Leong, Cheng Mee; Chen, Weisan; Forrester, John V; McMenamin, Paul G
• Is Part Of: Journal of leukocyte biology. Volume 97:Issue 1(2015)
• Page Start: 103
• Page End: 110
• Publication Date: 2014-11-21
• Subjects: innate inflammation -- Toll-like receptor -- anterior uveitis; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.3AB0414-216R
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : Sterile corneal inflammation induced by TLR7/8 and TLR9 agonists causes macrophage adherence to the corneal endothelium and giant macrophage formation in the connective tissue stroma. 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 −/−, Cx3 cr1 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.