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. |