Related Experiment Videos
The role of macrophages in Acanthamoeba keratitis
F van Klink1, W M Taylor, H Alizadeh
1Department of Ophthalmology, Leiden University Hospital, The Netherlands.
Purpose:
Macrophages are thought to be the first line of defense in many infectious diseases and are present in high numbers in corneas with Acanthamoeba keratitis. Conjunctival macrophage depletion was performed in an animal model of Acanthamoeba infection to determine the importance of macrophages in this disease.
Methods:
Selective elimination of macrophages was achieved by repeated subconjunctival injection of liposomes containing dichloromethylene diphosphonate in a Chinese hamster model of Acanthamoeba keratitis.
Results:
Macrophage depletion affected the incidence, severity, and chronicity of keratitis. The incidence of infection in normal animals was approximately 60% but rose to 100% on day 4 in animals treated with liposomes containing dichloromethylene diphosphonate (C12MDP-LIP). Moreover, the clinical appearance of the keratitis in the C12MDP-LIP group was much more severe than in animals treated with liposomes containing phosphate-buffered saline at all time points. There was also a major change in the chronicity of keratitis, with an earlier onset and a prolonged and chronic course in the C12MDP-LIP treated hamsters.
Conclusions:
The profound exacerbation of Acanthamoeba keratitis in hamsters treated with C12MDP-LIP strongly suggests that macrophages play an important role in corneal infection with Acanthamoeba trophozoites, probably by acting as a first line of defense and eliminating significant numbers of Acanthamoeba trophozoites.
Insights
Macrophages are crucial for defending against Acanthamoeba keratitis. Depleting macrophages worsened infection incidence, severity, and duration in a hamster model, highlighting their protective role.
Area of Science:
- Ophthalmology
- Immunology
- Infectious Diseases
Background:
- Macrophages are key immune cells, acting as the first line of defense in infectious diseases.
- Elevated macrophage presence is noted in corneas affected by Acanthamoeba keratitis.
Purpose of the Study:
- To investigate the role of macrophages in Acanthamoeba keratitis.
- To assess the impact of conjunctival macrophage depletion on experimental Acanthamoeba infection.
Main Methods:
- Utilized a Chinese hamster model of Acanthamoeba keratitis.
- Macrophages were selectively depleted using subconjunctival injections of liposomes containing dichloromethylene diphosphonate (C12MDP-LIP).
Main Results:
- Macrophage depletion increased infection incidence from approximately 60% to 100% in treated animals.
- Keratitis severity and chronicity were significantly exacerbated in C12MDP-LIP treated hamsters, with earlier onset and prolonged course.
- Control animals treated with phosphate-buffered saline liposomes showed less severe keratitis.
Conclusions:
- Macrophages play a vital role in controlling Acanthamoeba keratitis.
- The findings suggest macrophages act as a primary defense mechanism, eliminating Acanthamoeba trophozoites.
- Exacerbation of disease upon macrophage depletion underscores their importance in corneal immunity.