The delayed response of Toll-like receptors may relate to Pseudomonas aeruginosa keratitis exacerbating rapidly at the early stages of infection

Abstract

Keratitis caused by Pseudomonas aeruginosa is a potentially vision-threatening condition that requires prompt treatment to prevent vision loss. The recognition of infectious agents by the Toll-like receptor (TLR) system initiates primary innate and later adaptive immune responses. In this study, in late cases of corneal P. aeruginosa infection, the expression of TLR2, 4, 5 and 9 mRNA were all upregulated. In early infection cases, only TLR9 mRNA expression was upregulated. In late cases, the protein expression of TLR2, 4, 5, 9 and pIkappaB-alpha were elevated. In early cases, only TLR9 and pIkappaB-alpha expression were upregulated. Concentrations of IL-6 and IL-8 increased in infected corneas, especially in late cases. Myeloperoxidase (MPO) activity suggested that polymorphonuclear leukocyte (PMN) numbers were higher in late than in early stages of infection. The delayed response of TLRs may explain why P. aeruginosa infection exacerbates rapidly at the early infection stage. This finding may have important implications for the treatment of innate immunologic responses to corneal infections.