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Publication : Granulocytes in Ocular HSV-1 Infection: Opposing Roles of Mast Cells and Neutrophils.

First Author  Royer DJ Year  2015
Journal  Invest Ophthalmol Vis Sci Volume  56
Issue  6 Pages  3763-75
PubMed ID  26066745 Mgi Jnum  J:230958
Mgi Id  MGI:5766589 Doi  10.1167/iovs.15-16900
Citation  Royer DJ, et al. (2015) Granulocytes in Ocular HSV-1 Infection: Opposing Roles of Mast Cells and Neutrophils. Invest Ophthalmol Vis Sci 56(6):3763-75
abstractText  PURPOSE: The contributions of mast cells (MCs) to immunologic defense against pathogens in the eye are unknown. We have characterized pericorneal MCs as tissue-resident innate sentinels and determined their impact on the immune response to herpes simplex virus type-1 (HSV-1), a common ocular pathogen. METHODS: The impact of mast cells on the immune response to HSV-1 infection was investigated using MC-deficient Kit(W-sh) mice. Virus titers, inflammatory cytokine production, eicosanoid profiles, cellular immune responses, and ocular pathology were evaluated and compared with C57BL/6J mice during an acute corneal HSV-1 infection. RESULTS: Corneas of Kit(W-sh) mice have higher viral titers, increased edema, and greater leukocyte infiltration following HSV-1 infection. Following infection, cytokine profiles were slightly elevated overall in Kit(W-sh) mice. Eicosanoid profiles were remarkably different only when comparing uninfected corneas from both groups. Neutrophils within infected corneas expressed HSV-1 antigen, lytic genes, and served as a disease-causing vector when adoptively transferred into immunocompromised animals. Myeloid-derived suppressor cells did not infiltrate into the cornea or suppress the expansion, recruitment, or cytokine production by CD8+ T cells following acute HSV-1 infection. CONCLUSIONS: Collectively, these findings provide new insight into host defense in the cornea and the pathogenesis of HSV-1 infection by identifying previously unacknowledged MCs as protective innate sentinels for infection of the ocular surface and reinforcing that neutrophils are detrimental to corneal infection.
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