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

• Published in: Investigative ophthalmology & visual science Vol. 56; no. 6; pp. 3763 - 3775
• Main Authors: Royer, Derek J, Zheng, Min, Conrady, Christopher D, Carr, Daniel J J
• Format: Journal Article
• Language: English
• Published: United States The Association for Research in Vision and Ophthalmology 01.06.2015
• Subjects: Animals; Female; Granulocytes - immunology; Herpesvirus 1, Human; Immunology and Microbiology; Keratitis, Herpetic - immunology; Male; Mast Cells - immunology; Mice; Mice, Inbred C57BL; Neutrophils - immunology
• ISSN: 1552-5783; 0146-0404; 1552-5783
• DOI: 10.1167/iovs.15-16900

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. 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. 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. 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.