Abstract
Fusarium and Aspergillus species of mold are major causes of corneal infections in the United States and worldwide, resulting in severe visual impairment and blindness. As there is evidence for T cell responses to these pathogenic fungi in infected individuals, we examined the role of IL-17A (IL-17) and IFN-γ in murine models of fungal keratitis. We found that C57BL/6 mice given intratracheal or s.c. immunization of conidia prior to corneal infection exhibited enhanced fungal killing and lower corneal opacity compared with unimmunized mice. Protective immunity was associated with temporal recruitment of IL-17-producing neutrophils and Th17 and Th1 cells and dependent on production of IL-17 but not IFN-γ. Protection was also impaired in neutrophil-depleted and Rag2(-/-) mice. Together, the results of these studies identify an essential role for IL-17-producing neutrophils and Th17 cells in regulating the growth of fungal hyphae and the severity of corneal disease.
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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Aspergillus fumigatus / immunology*
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Aspergillus fumigatus / physiology
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Cornea / immunology*
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Cornea / microbiology
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DNA-Binding Proteins / deficiency
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / immunology
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Flow Cytometry
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Fusarium / immunology*
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Fusarium / physiology
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Host-Pathogen Interactions / immunology
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Humans
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Hyalohyphomycosis / immunology*
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Hyalohyphomycosis / microbiology
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Immunization / methods
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Interferon-gamma / immunology
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Interferon-gamma / metabolism
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Interleukin-17 / genetics
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Interleukin-17 / immunology*
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Interleukin-17 / metabolism
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Keratitis / immunology
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Keratitis / microbiology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Neutrophils / immunology*
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Neutrophils / metabolism
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Spleen / immunology
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Spleen / metabolism
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Spleen / pathology
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Spores, Fungal / immunology
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Th17 Cells / immunology*
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Th17 Cells / metabolism
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Time Factors
Substances
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DNA-Binding Proteins
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Interleukin-17
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Rag2 protein, mouse
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Interferon-gamma