Abstract
Purpose: :
The cornea is protected from pathogens by several physical barriers that are breached in microbial keratitis. Toll–like receptors (TLR) recognise pathogen–derived products and act as a first–line sentinel system against infection. We evaluated the expression of TLR in human corneal tissue taken from infected and non–infected eyes.
Methods: :
Immunohistochemical analysis was used to investigate expression of TLR2, TLR4, TLR6 and TLR9 in corneal buttons taken during penetrating keratoplasty from patients with severe acute and chronic microbial keratitis secondary to Gram+ve and Gram–ve bacteria and herpes simplex virus. Normal corneal sections from enucleated globes were used as controls. To determine the nature of cells expressing TLR, dual staining with CD68, and methyl–green pyronin (MGP) staining were performed.
Results: :
TLR2, TLR4, TLR6 and TLR9 were expressed in epithelial, stromal, and endothelial cells in infected corneas. The majority of the staining was on infiltrating cells, including macrophages (CD68+ve) plasma cells (MGP+ve) and neutrophils (morphology) located in the peripheral cornea and the site of infection. By comparison only TLR4 and TLR9 were expressed in the central region of normal cornea, and this was restricted to the endothelial layer.
Conclusions: :
TLR+ve cells in infected corneas appear to be blood–borne rather than resident, as there is no expression in normal central epithelial or stromal tissue. Although it is not clear how pathogens are initially recognised the data suggests that lack of TLR expression in the normal cornea may aid immune privilege
Keywords: keratitis • inflammation • cornea: basic science