Activation of neutrophils by autocrine IL-17A-IL-17RC interactions during fungal infection is regulated by IL-6, IL-23, RORγt and dectin-2.

Academic Article

Abstract

  • Here we identified a population of bone marrow neutrophils that constitutively expressed the transcription factor RORγt and produced and responded to interleukin 17A (IL-17A (IL-17)). IL-6, IL-23 and RORγt, but not T cells or natural killer (NK) cells, were required for IL-17 production in neutrophils. IL-6 and IL-23 induced expression of the receptors IL-17RC and dectin-2 on neutrophils, and IL-17RC expression was augmented by activation of dectin-2. Autocrine activity of IL-17A and its receptor induced the production of reactive oxygen species (ROS), and increased fungal killing in vitro and in a model of Aspergillus-induced keratitis. Human neutrophils also expressed RORγt and induced the expression of IL-17A, IL-17RC and dectin-2 following stimulation with IL-6 and IL-23. Our findings identify a population of human and mouse neutrophils with autocrine IL-17 activity that probably contribute to the etiology of microbial and inflammatory diseases.
  • Authors

    Keywords

  • Animals, Aspergillosis, Aspergillus, Autocrine Communication, Bone Marrow Cells, Cell Degranulation, Cells, Cultured, Cytotoxicity, Immunologic, Disease Models, Animal, Humans, Interleukin-17, Interleukin-23, Interleukin-6, Keratitis, Lectins, C-Type, Mice, Mice, Inbred C57BL, Mice, Knockout, Neutrophils, Nuclear Receptor Subfamily 1, Group F, Member 3, Reactive Oxygen Species, Receptors, Interleukin
  • Digital Object Identifier (doi)

    Author List

  • Taylor PR; Roy S; Leal SM; Sun Y; Howell SJ; Cobb BA; Li X; Pearlman E
  • Start Page

  • 143
  • End Page

  • 151
  • Volume

  • 15
  • Issue

  • 2