Granulocytes in Ocular HSV-1 Infection: Opposing Roles of Mast Cells and Neutrophils
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作者:
Royer, Derek J.
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Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73190 USAUniv Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73190 USA
Royer, Derek J.
[1
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Zheng, Min
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Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK USAUniv Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73190 USA
Zheng, Min
[2
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Conrady, Christopher D.
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Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73190 USAUniv Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73190 USA
Conrady, Christopher D.
[1
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Carr, Daniel J. J.
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Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73190 USA
Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK USAUniv Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73190 USA
Carr, Daniel J. J.
[1
,2
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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
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.
机构:
Univ Oklahoma, Hlth Sci Ctr, Microbiol & Immunol, Oklahoma City, OK USAUniv Oklahoma, Hlth Sci Ctr, Microbiol & Immunol, Oklahoma City, OK USA
Royer, Derek J.
Gurung, Hem Raj
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Univ Oklahoma, Hlth Sci Ctr, Microbiol & Immunol, Oklahoma City, OK USAUniv Oklahoma, Hlth Sci Ctr, Microbiol & Immunol, Oklahoma City, OK USA
Gurung, Hem Raj
Jinkins, Jeremy K.
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Univ Oklahoma, Hlth Sci Ctr, Ophthalmol, Oklahoma City, OK USAUniv Oklahoma, Hlth Sci Ctr, Microbiol & Immunol, Oklahoma City, OK USA
Jinkins, Jeremy K.
Halford, William
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Southern Illinois Univ, Sch Med, Med Microbiol Immunol & Cell Biol, Springfield, IL USAUniv Oklahoma, Hlth Sci Ctr, Microbiol & Immunol, Oklahoma City, OK USA
Halford, William
Carr, Daniel J.
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Univ Oklahoma, Hlth Sci Ctr, Microbiol & Immunol, Oklahoma City, OK USA
Univ Oklahoma, Hlth Sci Ctr, Ophthalmol, Oklahoma City, OK USAUniv Oklahoma, Hlth Sci Ctr, Microbiol & Immunol, Oklahoma City, OK USA
机构:
Cedars Sinai Med Ctr, Ctr Neurobiol & Vaccine Dev, Burns & Allen Res Inst, Ophthalmol Res Labs, Los Angeles, CA 90048 USACedars Sinai Med Ctr, Ctr Neurobiol & Vaccine Dev, Burns & Allen Res Inst, Ophthalmol Res Labs, Los Angeles, CA 90048 USA
Mott, Kevin R.
Wechsler, Steven L.
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机构:
Univ Calif Irvine, Gavin S Herbert Eye Inst, Irvine, CA USA
Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92717 USA
Univ Calif Irvine, Ctr Virus Res, Irvine, CA USACedars Sinai Med Ctr, Ctr Neurobiol & Vaccine Dev, Burns & Allen Res Inst, Ophthalmol Res Labs, Los Angeles, CA 90048 USA
Wechsler, Steven L.
Ghiasi, Homayon
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Cedars Sinai Med Ctr, Ctr Neurobiol & Vaccine Dev, Burns & Allen Res Inst, Ophthalmol Res Labs, Los Angeles, CA 90048 USACedars Sinai Med Ctr, Ctr Neurobiol & Vaccine Dev, Burns & Allen Res Inst, Ophthalmol Res Labs, Los Angeles, CA 90048 USA
机构:
Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, CSIC, UAM, C Nicolas Cabrera 1, Madrid 28049, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, SpainUniv Autonoma Madrid, Ctr Biol Mol Severo Ochoa, CSIC, UAM, C Nicolas Cabrera 1, Madrid 28049, Spain
Llorente, Patricia
Mejias, Victor
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Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, CSIC, UAM, C Nicolas Cabrera 1, Madrid 28049, SpainUniv Autonoma Madrid, Ctr Biol Mol Severo Ochoa, CSIC, UAM, C Nicolas Cabrera 1, Madrid 28049, Spain
Mejias, Victor
Sastre, Isabel
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机构:
Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, CSIC, UAM, C Nicolas Cabrera 1, Madrid 28049, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, SpainUniv Autonoma Madrid, Ctr Biol Mol Severo Ochoa, CSIC, UAM, C Nicolas Cabrera 1, Madrid 28049, Spain
Sastre, Isabel
Recuero, Maria
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机构:
Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, CSIC, UAM, C Nicolas Cabrera 1, Madrid 28049, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Hosp La Paz IdIPaz, Inst Invest Sanitaria, Madrid, SpainUniv Autonoma Madrid, Ctr Biol Mol Severo Ochoa, CSIC, UAM, C Nicolas Cabrera 1, Madrid 28049, Spain
Recuero, Maria
Aldudo, Jesus
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机构:
Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, CSIC, UAM, C Nicolas Cabrera 1, Madrid 28049, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Hosp La Paz IdIPaz, Inst Invest Sanitaria, Madrid, SpainUniv Autonoma Madrid, Ctr Biol Mol Severo Ochoa, CSIC, UAM, C Nicolas Cabrera 1, Madrid 28049, Spain
Aldudo, Jesus
Bullido, Maria J.
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机构:
Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, CSIC, UAM, C Nicolas Cabrera 1, Madrid 28049, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Hosp La Paz IdIPaz, Inst Invest Sanitaria, Madrid, SpainUniv Autonoma Madrid, Ctr Biol Mol Severo Ochoa, CSIC, UAM, C Nicolas Cabrera 1, Madrid 28049, Spain