Innate Resistance of Corneas to Pathogen Infections

With great interest, I read the paper by Alarcon et al. ¹ that appears in the March 2011 issue. In this article, the mechanisms for the corneal epithelium to innately resist bacterial adherence and traversal were studied. In brief, the authors found that pretreatment of blotted corneas with ethylene glycol tetraacetic acid (EGTA) enabled the attached Pseudomonas aeruginosa to penetrate the epithelial layers. They further showed that EGTA treatment disrupted the clusters of ZO-1 protein between epithelial cells, implying the loss of the tight junctions between the cells. A conclusion that “corneal epithelial defenses limiting traversal by adherent bacteria include EGTA-sensitive factors and SP-D” was drawn in this article. In other words, the loss of the innate resistance of corneas to bacterial infection could happen when a pattern of constituent arrangement occurs. 

In a previous study, my team reported that BALB/c mice developed typical keratitis when Candida albicans spores were inoculated into the stroma. ² However, nude mice of BALB/c background did not develop Candida keratitis when similarly challenged. ³ Besides implying that T cells play a critical role in the development of Candida keratitis, our recent observation also demonstrated that the murine cornea, or the stroma specifically, has the innate ability to suppress spore budding or fungal growth. Otherwise, the inoculated Candida spores would transform into hyphae, continue to replicate, and cause keratitis. We had originally thought that the innate resistance of the corneal stroma is mediated by certain soluble factors, and we therefore looked into whether murine corneal homogenates manifest any suppressive effects on the replication of Candida spores in culture in vitro. Surprisingly and contrary to our expectations, the murine homogenates enhanced spore budding and replication in vitro. ⁴ In our latest paper, we concluded that the innate resistance of the corneal stroma to Candida spore expansion relies on the specific structure of the corneal stroma. ⁴ Although the pathogens (bacteria and fungi, respectively) used by Alarcon et al. were different from those that we used, we think the findings in these two papers are complementary in some ways.