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H. Ghiasi, K. Mott; Role of APCs in Control of Primary and Latent Ocular HSV-1 Infection in Mice. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2826. doi: https://doi.org/.
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To determine the effect of APCs depletions on HSV-1 replication in the eye and on the establishment of latency in trigeminal ganglia (TG) of immunized and ocularly infected mice.
BALB/c and BALB/c-DTR mice were immunized with five HSV-1 glycoprotein DNA genes (5gP DNA) or vector control DNA. Avirulent HSV-1 strain KOS was used as positive vaccine control. Immunized mice were depleted of their macrophages, DCs, or both by injection of dichloromethylene diphosphonate (Cl2MDP) and/or diphtheria toxin (DT). Following ocular infection with HSV-1 strain McKrae, virus replication in the eye, TG, and eye disease were determined. The copy numbers of latency associated transcript (LAT), gB, CD4+ T cell, and CD8+ T cell transcripts in the corneas and TGs on days 5 and 30 post infection (PI) were determined by TaqMan RT-PCR.
Depletion of macrophages in immunized mice increased HSV-1 replication in the eye of infected mice between day 1 and 5 PI, while depletion of DCs had no effect on virus replication in the eye. Depletion of macrophages or DCs did not alter the HSV-1 induced death or corneal scarring in immunized or control mice. Macrophage depletion had no effect on the establishment of latency in immunized mice, as the TG from both depleted and mock depleted mice were negative for the presence of the LAT transcript. In contrast, depletion of DCs resulted in reduction of LAT expression in TG of latent mice.
In immunized mice during primary HSV-1 infection, macrophages, but not DCs, play an important role in vaccine efficacy against HSV-1 replication in the eye and blepharitis. During the latent stage of HSV-1 infection, macrophage depletion failed to have any observable effect on HSV-1 latency in the TG of infected mice, while there was an inverse correlation between presence of DCs and LAT expression in latently infected mice.
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