4.6 Article

Aspergillus and Fusarium Corneal Infections Are Regulated by Th17 Cells and IL-17-Producing Neutrophils

Journal

JOURNAL OF IMMUNOLOGY
Volume 192, Issue 7, Pages 3319-3327

Publisher

AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1302235

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Funding

  1. National Institutes of Health [F32EY022278, F31EY019841, RO1 EY018612, P30 EY011373]
  2. Research to Prevent Blindness Foundation
  3. Ohio Lions Eye Research Foundation

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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-gamma 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-gamma. 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.

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