微生物および生化学技術ジャーナル

概要

Pseudomonas Keratitis, a Review of Where Wehave Been and What Lies Ahead

Alicia Eby M and Linda Hazlett D

Microbial keratitis can result in significant vision loss secondary to corneal scarring or surface irregularity. If untreated, corneal perforation and endophthalmitis can occur, resulting in loss of the eye. Damage to the cornea can occur in as little as 24 hrs and the most aggressive infections are often caused by P. aeruginosa which is a highly virulent opportunistic pathogen. This bacterium is highly effective at evading the immune response and blunting it via several mechanisms. Normally the innate immune system provides defense with neutrophils which are recruited within as little as 6-12 hrs of infection travelling from limbal vessels via the tear film to the site of the infection. These cells play a critical role in limiting bacterial proliferation as well as protecting host tissue from destruction, but if they persist locally they are detrimental, inducing additional tissue damage. Evasion is aided in part due to the bacterial glycocalyx which functions to inhibit migration and function of neutrophils. Beyond this first line of defense, the complex story unravels involving secreted exotoxins S, T and U, the role of TLRs, chemokines and cytokines including interleukins 1, 6, 10, 12, 17 and 18, IFN-γ as well as CD4+ T cells, antigen presenting cells (Langerhans cells) and macrophages. With a complex interplay between bacteria and host, infection with P. aeruginosa has a hallmark ability to incite an exuberant immune response, propagating local tissue damage. It is facile to appreciate just how difficult it has been to target precise susceptibilities, treatment strategies and models of pathogenesis, given the elaborate mechanisms involved in both bacterial action and more importantly host inflammation. Herein we will review some of the major breakthroughs in our understanding of the pathogenesis of this bacterium and discuss recent novel therapeutic targets.