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

被引:46
|
作者
Royer, Derek J. [1 ]
Zheng, Min [2 ]
Conrady, Christopher D. [1 ]
Carr, Daniel J. J. [1 ,2 ]
机构
[1] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73190 USA
[2] Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK USA
基金
美国国家卫生研究院;
关键词
mast cell; herpes simplex virus type-1; innate immunity; cornea; SUPPRESSOR-CELLS; VIRUS-REPLICATION; HUMAN CORNEAL; PROSTAGLANDIN D-2; LIPID MEDIATORS; HEPOXILIN A(3); INFLAMMATION; RECRUITMENT; LUNG; RESOLUTION;
D O I
10.1167/iovs.15-16900
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
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 KitW-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 KitW-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 KitW-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.
引用
收藏
页码:3763 / 3775
页数:13
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