TLR9 和 TLR7/8 的激活可诱导小鼠角膜形成角膜内沉着物和巨大巨噬细胞。
TLR9 and TLR7/8 activation induces formation of keratic precipitates and giant macrophages in the mouse cornea.
机构信息
*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
*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.
出版信息
J Leukoc Biol. 2015 Jan;97(1):103-10. doi: 10.1189/jlb.3AB0414-216R. Epub 2014 Nov 21.
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.
巨噬细胞在内眼角膜表面的黏附和在基质中形成 MGCs 是角膜感染后慢性炎症的常见标志。为了确定巨噬细胞黏附和（临床上称为 KP）以及巨细胞的形成是否是特定 TLR 配体激活固有免疫的特异性标志，我们在 TLR 介导的角膜炎症的小鼠模型中检查了巨噬细胞的激活情况。我们清除角膜上皮，并将高度纯化的 TLR 配体单次局部应用于 TLR7(-/-)、TLR9(-/-)、Cx3cr1(gfp/+)、CD11c(eYFP)和 IL-4(-/-) 小鼠的角膜。在治疗后 1 周，评估角膜中的巨噬细胞激活和表型。TLR2、TLR3、TLR4 和 TLR5 配体的处理导致治疗后 1 周中央角膜中激活的基质巨噬细胞数量增加。然而，TLR9 配体 CpG-ODN 和 TLR7/8 配体 R848/Resiquimod 的处理导致巨噬细胞在内皮角膜上的积累，并在角膜基质中形成多核巨巨噬细胞。我们认为，巨细胞的形成是许多组织中肉芽肿形成的特征，可能是 TLR9 和 TLR7/8 介导的巨噬细胞激活的独特特征。
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