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Susmit Suvas, Brandon Twardy, Rudragouda Channappanavar; Differential Role of Neutrophils and Inflammatory Monocytes in Herpetic Stromal Keratitis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2910.
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To determine if neutrophils (CD11b+F4/80-Ly6G+) or inflammatory monocytes (CD11b+F4/80+Ly6G-Ly6C+) differentially regulate the corneal viral load and lesion severity after ocular herpes simplex virus-1 (HSV-1) infection of C57BL/6 mice.
C57BL/6 mice were euthanized at regular intervals of time after ocular HSV-1 infection. Corneal samples were Collagenase digested and flow cytometery was performed to ascertain the influx of neutrophils and inflammatory monocytes during pre-clinical and clinical phase of HSK. Next, C57BL/6 mice were depleted of neutrophils in vivo starting before or 7 days after ocular HSV-1 infection while using anti-Ly6G (1A8) monoclonal antibody. Inflammatory monocytes were depleted in vivo before or 7 days after ocular HSV-1 infection with either anti-Gr1 monoclonal antibody or clodronate liposomes. Viral load in the corneas of control and depleted groups was determined by plaque assay. Corneal lesion severity was ascertained by measuring the corneal opacity and angiogenesis by hand-held slit lamp microscope.
Kinetics of CD11b+ cells after ocular HSV-1 infection demonstrated the predominance of monocytes (F4/80+Ly6G-) in the cornea during pre-clinical phase of HSK. However, during clinical phase of HSK, majority of CD11b+ cells in the inflamed cornea had F4/80-Ly6G+ phenotype (neutrophils). Depletion of neutrophils during pre-clinical phase of HSK did not result in a significant difference in the corneal viral load when compared to isotype treated HSV-1 infected C57BL/6 mice. However, depletion of neutrophils during clinical phase of HSK (7 days after infection) resulted in a significant decrease in the corneal lesion severity in comparison to the eyes from isotype treated infected mice. On the other hand, depletion of inflammatory monocytes during pre-clinical phase of HSK resulted in a significant increase in the corneal viral load in comparison to HSV-1 infected control group. Clodronate liposome treatment during clinical phase of HSK to deplete monocytes did not result in a significant difference in corneal lesion severity when compared to PBS treated infected mice group.
Our results demonstrate that inflammatory monocytes but not neutrophils are largely involved in clearing the virus from the infected corneas of C57BL/6 mice. On the other hand, neutrophils but not inflammatory monocytes are involved in orchestrating the corneal tissue damage in HSK.
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