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Hao Cheng, Terrence M. Tumpey, Herman F. Staats, Nico van Rooijen, John E. Oakes, Robert N. Lausch; Role of Macrophages in Restricting Herpes Simplex Virus Type 1 Growth after Ocular Infection. Invest. Ophthalmol. Vis. Sci. 2000;41(6):1402-1409.
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purpose. To investigate the role macrophages play in controlling herpes simplex
virus (HSV)-1 replication after infection of the murine cornea.
methods. Macrophage depletion in selected tissues before or after virus
infection was achieved by repeated subconjunctival (SCJ) and/or
intravenous (IV) injection of liposomes containing dichloromethylene
diphosphonate (L-Cl2MDP). Controls received liposomes
containing phosphate-buffered saline (L-PBS). The efficiency of
depletion was evaluated by histologic examination. Virus content in
infected tissues was determined by standard plaque assay. Delayed-type
hypersensitivity (DTH) responsiveness was assessed using the
ear-swelling assay. Antibody isotype responses to virus antigens and
cytokine production were monitored by enzyme-linked immunosorbent
results. Balb/c mice given SCJ injection of L-Cl2MDP 4 and 2 days
before HSV-1 corneal infection were found to have ocular virus titers
as much as 105-fold higher than that seen in the
L-PBS–treated controls 8 days after infection. When
L-Cl2MDP treatment was delayed until 2 and 4 days after
infection, virus titers in the eye were analogous to those in the
control animals. Subconjunctival and submandibular lymph node
macrophages in mice given local (SCJ) L-Cl2MDP pretreatment
were profoundly reduced, whereas the number of corneal Langerhans’
cells and lymph node dendritic cells remained unchanged. Local
L-Cl2MDP pretreatment was associated with significantly
reduced DTH responsiveness to HSV-1 antigen, and an alteration in
selected antibody isotype production. Depletion of macrophages in the
subconjunctival tissue before corneal infection was not accompanied by
enhanced virus growth at early times (2 or 4 days) after infection.
conclusions. Macrophages play an important role in restricting HSV-1 growth after
corneal infection. These cells appear to be required for the
development of an acquired immune response, presumably by functioning
in antigen processing and presentation. The hypothesis that macrophages
are major participants in innate immunity to HSV-1 corneal infection
was not supported.
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