Abstract
Herpes simplex virus (HSV) infection of the cornea culminates in an immunopathological lesion (stromal keratitis--SK) that impairs vision. This report shows that HSV infection results in IL-23 up-regulation, but if this response fails to occur, as was noted in p19-/- mice, the severity of lesions, their incidence and the level of viral induced angiogenesis were significantly increased compared to wild-type (WT) animals (p<0.05). The higher disease severity in p19-/- mice appeared to be the consequence of an increased IL-12 response that in turn led to the induction of higher numbers of IFN-gamma producing CD4(+)T cells, the principal orchestrators of SK. Our results indicate that the severity of HSV induced immunopathological lesions may be mainly the consequence of IL-12 driven Th1 T cell reactions rather than the action of IL-17 producing cells controlled by IL-23.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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Cell Division
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Cornea / immunology
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Cornea / pathology
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Cornea / virology
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Female
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Herpes Simplex / immunology*
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Herpes Simplex / pathology
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Herpes Simplex / virology
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Herpesvirus 1, Human / pathogenicity
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Herpesvirus 1, Human / physiology*
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Inflammation / pathology
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Interferon-gamma / biosynthesis
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Interleukin-12 / biosynthesis
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Interleukin-23 / chemistry
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Interleukin-23 / metabolism*
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Keratitis, Herpetic / immunology*
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Keratitis, Herpetic / pathology*
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Keratitis, Herpetic / virology
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Lymph Nodes / immunology
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Molecular Weight
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Protein Subunits / deficiency
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Protein Subunits / genetics
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Spleen / immunology
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Virulence
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Virus Replication
Substances
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Interleukin-23
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Protein Subunits
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Interleukin-12
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Interferon-gamma