Macrophage-depletion influences the course of murine HSV-1 keratitis.
OBJECTIVE
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.
Bauer
D
D
Department of Ophthalmology, University of Essen, Essen, Germany.
Mrzyk
S
S
van Rooijen
N
N
Steuhl
K P
KP
Heiligenhaus
A
A
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D002452:Cell Count / Q000187:drug effects; D018450:Disease Progression; D005260:Female; D018259:Herpesvirus 1, Human / Q000235:genetics; D007150:Immunohistochemistry; D016849:Keratitis, Herpetic / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D008081:Liposomes / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010948:Viral Plaque Assay
D000943:Antigens, Differentiation; D008081:Liposomes; C036763:monocyte-macrophage differentiation antigen