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Dhong Hyun Tony Lee, Homayon Ghiasi; Role of M1 and M2 macrophages in herpes simplex virus-1 infectivity in vitro and in vivo. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3616.
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© ARVO (1962-2015); The Authors (2016-present)
Ocular herpes simplex virus 1 (HSV-1) infection is a major cause of eye disease and blindness in the United States. We have previously reported that macrophages are the most dominant infiltrates in the corneas of ocularly infected mice. To better understand the relationship between macrophage and HSV-1 infection, we assessed the relative impact of M1 and M2 macrophage polarization on the HSV-1 responses in vitro and in vivo.
Macrophages from female C57BL/6 mice were harvested, polarized with either M1 or M2 agonists followed by infection with the HSV-1 virus. Plaque assay was performed to measure HSV-1 infectivity in the M1- and M2-polarized macrophages. Luminex assay was performed to measure the changes in the profile of cytokine/chemokine produced in the infected cells. In addition, mice were injected with plasmid DNAs to coax the macrophages toward the M1 or M2 polarized state. The phenotype of macrophages in vivo were confirmed by flow cytometry. Three weeks after the third injection, mice were infected ocularly with the wild type HSV-1 strain McKrae. Virus replication in the eye and the level of latency in the trigeminal ganglia (TG) of the infected mice were determined on day 28 post infection.
Plaque assay results showed that HSV-1 infectivity was dramatically decreased in the M1 polarized macrophages compared to the unstimulated control and M2 macrophages. Luminex assay results showed that HSV-1 infection significantly altered the profile of cytokine expression in the M1- versus M2- polarized macrophages. Infected M1 macrophages showed increased production of inflammatory cytokines compared with infected M2 macrophages. While mouse survival and corneal scarring were similar in mice with M1- or M2-polarized macrophages, virus replication and latency was lower in mice with M2-polarized macrophages compared with mice with M1-polarized macrophages.
Our findings demonstrate a novel approach to further reduce viral replication in the eye and latency in the TG by modulating immune components, particularly by altering the phenotype of macrophages. We suggest that inclusion of cellular factor(s) with a cocktail of HSV-1 glycoproteins to coax responses of macrophages toward M2 polarization, as compared to the M1 polarization, may further improve vaccine efficacy against ocular HSV-1 replication and latency-reactivation in the ocularly infected mice.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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