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Updated: Aug 15, 2026
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Macrophage-depletion influences the course of murine HSV-1 keratitis
D Bauer1, S Mrzyk, N van Rooijen
1Department of Ophthalmology, University of Essen, Essen, Germany.
Purpose:
Herpes simplex virus type 1 infection of the cornea induces an immune-mediated disease termed "herpes stromal keratitis" (HSK) that is a major cause of blindness. In this study we investigated the influence of macrophage depletion by Cl(2) MDP encapsulated in liposomes (Cl(2) MDP-LIP) on the course of HSV-1 keratitis.
Methods:
The corneas of BALB/c mice were infected with 10(5) PFU of HSV-1 (KOS strain). Mice groups received sub-conjunctival PBS or Cl( 2) MDP-LIP injections 7 and 2 days prior to infection. The eyes were studied clinically, histologically and immunohistochemically with F4/80 antibody at various time points after treatment. Clearance of the virus from the HSV-infected eyes was measured with a standard plaque assay.
Results:
After subconjunctival Cl(2) MDP-LIP treatment, the HSV-1-induced epithelial keratitis was more severe (P < 0.05). The virus titers were significantly higher after macrophage depletion (day 7, P < 0.005). Stromal keratitis developed in 78.6% of HSV-1 infected PBS treated control mice ( n = 14) by day 14 after infection. By subconjunctival Cl(2) MDP-LIP treatment (n = 14) the incidence of stromal keratitis was reduced to 42.9%, and the keratitis was less severe (P < 0.05).
Conclusions:
The data demonstrate an influence of macrophages on the course of HSV-1 keratitis in mice. Macrophage depletion influence the viral replication in the cornea and the immune-mediated process of HSK.
Insights
Depleting macrophages in mice reduced the severity of herpes stromal keratitis (HSK) caused by herpes simplex virus type 1 (HSV-1). This macrophage depletion also impacted viral replication in the cornea, influencing the immune response in HSK.
Area of Science:
- Ophthalmology
- Immunology
- Virology
Background:
- Herpes simplex virus type 1 (HSV-1) infection can lead to herpes stromal keratitis (HSK), a significant cause of blindness.
- HSK is an immune-mediated disease affecting the cornea.
Purpose of the Study:
- To investigate the effect of macrophage depletion on the progression of HSV-1 keratitis.
- To understand the role of macrophages in HSV-1-induced ocular disease.
Main Methods:
- BALB/c mice were infected with HSV-1.
- Macrophage depletion was induced using Cl(2) MDP encapsulated in liposomes (Cl(2) MDP-LIP) via subconjunctival injections.
- Clinical, histological, and immunohistochemical analyses were performed, along with viral plaque assays.
Main Results:
- Macrophage depletion exacerbated epithelial keratitis and increased HSV-1 titers in the cornea.
- However, subconjunctival Cl(2) MDP-LIP treatment significantly reduced the incidence and severity of stromal keratitis.
- HSK incidence decreased from 78.6% in controls to 42.9% in treated mice.
Conclusions:
- Macrophages play a crucial role in the pathogenesis of HSV-1 keratitis.
- Macrophage depletion influences viral replication and the immune-mediated inflammatory process in HSK.
