Derek J Royer1, Min Zheng2, Christopher D Conrady1, Daniel J J Carr3. 1. Department of Microbiology and Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States. 2. Department of Ophthalmology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States. 3. Department of Microbiology and Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States 2Department of Ophthalmology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States.
Abstract
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.
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.
Authors: Gregory M Frank; Kristine-Ann G Buela; Dawn M Maker; Stephen A K Harvey; Robert L Hendricks Journal: J Immunol Date: 2011-12-30 Impact factor: 5.422
Authors: D F Anderson; J D MacLeod; S M Baddeley; A S Bacon; J I McGill; S T Holgate; W R Roche Journal: Clin Exp Allergy Date: 1997-09 Impact factor: 5.018
Authors: Daniel J J Carr; Grzegorz B Gmyrek; Adrian Filiberti; Amanda N Berube; William P Browne; Brett M Gudgel; Virginie H Sjoelund Journal: Immunohorizons Date: 2020-10-09
Authors: Sohyun Jeon; Alexander M Rowe; Kate L Carroll; Stephen A K Harvey; Robert L Hendricks Journal: J Immunol Date: 2018-04-18 Impact factor: 5.422
Authors: Daniela Michlmayr; Susana V Bardina; Carlos A Rodriguez; Alexander G Pletnev; Jean K Lim Journal: J Immunol Date: 2016-04-29 Impact factor: 5.422
Authors: Derek J Royer; Hem R Gurung; Jeremy K Jinkins; Joshua J Geltz; Jennifer L Wu; William P Halford; Daniel J J Carr Journal: J Virol Date: 2016-05-12 Impact factor: 5.103