Abstract
Staphylococcus aureus is one of the most common pathogens causing keratitis. Surfactant protein D (SP-D) plays a critical role in host defense and innate immunity. In order to investigate the role of SP-D in ocular S. aureus infection, the eyes of wild-type (WT) and SP-D knockout (SP-D KO) C57BL/6 mice were infected with S. aureus (107 CFU/eye) in the presence and absence of cysteine protease inhibitor(E64).Bacterial counts in the ocular surface were examined 3, 6, 12, 24 hrs after infection. Bacterial phagocytosis by neutrophils and bacterial invasion in ocular epithelial cells were evaluated quantitatively. S. aureus-induced ocular injury was determined with corneal fluorescein staining. The results demonstrated that SP-D is expressed in ocular surface epithelium and the lacrimal gland; WT mice had increased clearance of S. aureus from the ocular surface (p<0.05) and reduced ocular injury compared with SP-D KO mice. The protective effects of SP-D include increased bacterial phagocytosis by neutrophils (p<0.05) and decreased bacterial invasion into epithelial cells (p<0.05) in WT mice compared to in SP-D KO mice. In the presence of inhibitor (E64), WT mice showed enhanced bacterial clearance (p<0.05) and reduced ocular injury compared to absent E64 while SP-D KO mice did not. Collectively, we concluded that SP-D protects the ocular surface from S. aureus infection but cysteine protease impairs SP-D function in this murine model, and that cysteine protease inhibitor may be a potential therapeutic agent in S. aureus keratitis.
Highlights
Staphylococcus aureus is one of the most important pathogens causing keratitis, a disease that can lead to serious vision loss [1,2]
The clearance of S. aureus was assessed by counting bacterial colony-forming units (CFU) in the tear fluid collected from infected WT mice that ocular surface was inoculated with 107 CFU of bacteria
The results showed that Surfactant protein D (SP-D) KO mice had significantly higher CFUs of bacteria (p
Summary
Staphylococcus aureus is one of the most important pathogens causing keratitis, a disease that can lead to serious vision loss [1,2]. The mucin layer and intercellular tight junctions of corneal epithelium are the main two barriers that prevent S. aureus from binding to and penetrating into the cornea. A disruption of these barriers can significantly increase the susceptibility to S. aureus infection and results in S. aureus keratitis [3,4]. The innate immune system, other than the barriers mentioned above, is the first-line defense that contributes to maintaining a healthy ocular surface [5,6,7]. An efficient innate immune system is critical for corneal protection from.
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