Macrophage-depletion influences the course of murine HSV-1 keratitis

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 CI,MDP encapsulated in liposomes (Cl2MDP-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 subconjunctival PBS or Cl2MDP-LIP injections 7 anti 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 Cl2MDP-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 Cl2MDP-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.