TLR4 Contributes to the Host Response to Klebsiella Intraocular Infection

Abstract

Purpose/Aim: Klebsiella pneumoniae causes a blinding infection called endogenous endophthalmitis. The role of innate immune recognition of K. pneumoniae in the eye during infection is not known. We hypothesized that intraocular recognition of K. pneumoniae was mediated by Toll-like receptor (TLR)-4 and may be dependent on MagA-regulated hypermucoviscosity.

Materials and Methods: Experimental endophthalmitis was induced in C57BL/6J or TLR4^−/− mice by intravitreal injection of 100 CFU of wild type or ΔmagA K. pneumoniae. Infection and inflammation were quantified by determining viable K. pneumoniae per eye, retinal responses via electroretinography, myeloperoxidase activity of infiltrating neutrophils and the proinflammatory cytokine and chemokine response.

Results: C57BL/6J and TLR4^−/− mice could not control intraocular wild-type K. pneumoniae growth. TLR4^−/− mice were less able than C57BL/6J to control the intraocular growth of ΔmagA K. pneumoniae. Retinal function testing suggested that infection with ΔmagA K. pneumoniae resulted in less retinal function loss. There was a TLR4-dependent delay in initial neutrophil recruitment, regardless of the infecting organism. The proinflammatory cytokine/chemokine data supported these results. These findings were not due to an inability of TLR4^−/− neutrophils to recognize or kill K. pneumoniae.

Conclusions: These studies suggest that TLR4 is important in the early intraocular recognition and host response to K. pneumoniae. However, the role of MagA in TLR4-mediated intraocular recognition and subsequent inflammation is less clear.

• Endophthalmitis
• eye
• hypermucoviscosity
• Klebsiella pneumoniae
• Toll-like receptor 4 (TLR4)

Acknowledgements

The authors thank Phil Coburn, Ph.D. (University of Oklahoma Health Sciences Center) for helpful discussion, Mark Dittmar (Dean A. McGee Eye Institute Animal Research Facility) and Elizabeth B. Christy (Dean A. McGee Eye Institute) for their invaluable technical assistance, and Paula Pierce (Excalibur Pathology, Moore, OK) for histology expertize.