The Role of CXC Chemokine Receptor Two in Pseudomonas aeruginosa and Staphylococcus aureus Corneal Infection

Abstract

Purpose:: Despite the use of antibiotics for microbial keratitis, the host inflammatory response continues to cause damage to the cornea, which may lead to blindness. CXC receptor 2 binding chemokines have been implicated in the pathogenesis of P. aeruginosa keratitis, however its exact role in P. aeruginosa keratitis and its role in S. aureus keratitis remains to be elucidated.

Methods:: Corneas of CXC receptor 2 knockout and wildtype mice (Cmkar -/- & Cmkar +/+) were scratched and 1 x 10⁸ or and 2 x 10⁶ colony forming units/mL of S. aureus or P.aeruginosa were added to corneas respectively, contralateral eyes served as a scratch control. Twenty-four hours post-infection, mice were sacrificed and eyes harvested for enumeration of bacteria, myeloperoxidase levels (MPO), chemokines and LTB₄.

Results:: For S. aureus infected eyes Cmkar -/- had greater than 10 fold more bacteria than WT mice. Levels of chemokines (KC, MIP-2 & MCP-1) were significantly elevated in gko mice (p < 0.05). For P. aeruginosa eyes Cmkar -/- had 20-100 fold more bacteria than WT mice. Levels of chemokines (KC, MIP-2 & LTB₄) were significantly elevated in gko mice (p < 0.05). No differences in MPO levels between gko and WT mice for both bacterial strains.

Conclusions:: A lack of CXC receptor 2 leads to an inability to control bacterial numbers in spite of similar levels of infiltrating cells as a result of compensatory expression of chemokines. This may indicate a pivotal role of the CXC2 receptor in neutrophil activation.

Keywords: inflammation • keratitis • cytokines/chemokines