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Role of macrophages in restricting herpes simplex virus type 1 growth after ocular infection
H Cheng1, T M Tumpey, H F Staats
1Department of Microbiology and Immunology, College of Medicine, University of South Alabama, Mobile, USA.
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 assay.
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 10(5)-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.
Insights
Macrophages are crucial for limiting herpes simplex virus type 1 (HSV-1) replication in the cornea. Depleting macrophages before infection significantly increases viral load, highlighting their role in controlling HSV-1.
Area of Science:
- Immunology
- Virology
- Ophthalmology
Background:
- Herpes simplex virus type 1 (HSV-1) establishes lifelong infections, often manifesting as ocular disease.
- Macrophages are key immune cells involved in host defense against viral pathogens.
- Understanding the specific roles of immune cells in ocular HSV-1 infection is critical for developing effective treatments.
Purpose of the Study:
- To elucidate the role of macrophages in controlling HSV-1 replication within the murine cornea.
- To determine if macrophages are involved in innate or adaptive immune responses to HSV-1 corneal infection.
Main Methods:
- Macrophage depletion was induced using liposomes containing dichloromethylene diphosphonate (L-Cl2MDP) administered via subconjunctival (SCJ) or intravenous (IV) routes before or after HSV-1 infection.
- Viral titers in infected corneas were quantified using plaque assays.
- Delayed-type hypersensitivity (DTH) responses, antibody isotype profiles, and cytokine production were assessed to evaluate immune responses.
Main Results:
- Pre-infection SCJ administration of L-Cl2MDP led to a 10(5)-fold increase in ocular HSV-1 titers by day 8 post-infection.
- Depletion of macrophages in subconjunctival tissue before infection did not enhance early viral growth.
- Macrophage depletion resulted in reduced DTH responsiveness and altered antibody isotype production, suggesting a role in adaptive immunity.
Conclusions:
- Macrophages play a significant role in restricting HSV-1 replication following corneal infection.
- These cells are essential for the development of an acquired immune response, likely through antigen processing and presentation.
- Macrophages do not appear to be major mediators of innate immunity against HSV-1 in the context of corneal infection.