Neutrophils produce interleukin 17A (IL-17A) in a dectin-1- and IL-23-dependent manner during invasive fungal infection

Infect Immun. 2011 Oct;79(10):3966-77. doi: 10.1128/IAI.05493-11. Epub 2011 Aug 1.

Abstract

We have previously reported that compromised interleukin 17A (IL-17A) production in the lungs increased susceptibility to infection with the invasive fungal pathogen Aspergillus fumigatus. Here we have shown that culturing lung cells from A. fumigatus-challenged mice ex vivo demonstrated Dectin-1-dependent IL-17A production. In this system, neutralization of IL-23 but not IL-6, IL-1β, or IL-18 resulted in attenuated IL-17A production. Il23 mRNA expression was found to be lower in lung cells from A. fumigatus-challenged Dectin-1-deficient mice, whereas bone marrow-derived dendritic cells from Dectin-1-deficient mice failed to produce IL-23 in response to A. fumigatus in vitro. Addition of recombinant IL-23 augmented IL-17A production by wild-type (WT) and Dectin-1-deficient lung cells, although the addition of IL-6 or IL-1β did not augment the effect of IL-23. Intracellular cytokine staining of lung cells revealed lower levels of CD11b(+) IL-17A(+) and Ly-6G(+) IL-17A(+) cells in A. fumigatus-challenged Dectin-1-deficient mice. Ly-6G(+) neutrophils purified from the lungs of A. fumigatus-challenged Dectin-1-deficient mice displayed lower Il17a mRNA expression but surprisingly had intact Rorc and Rora mRNA expression. We further demonstrated that Ly-6G(+) neutrophils required the presence of myeloid cells for IL-17A production. Finally, upon in vitro stimulation with A. fumigatus, thioglycolate-elicited peritoneal neutrophils were positive for intracellular IL-17A expression and produced IL-17A in a Dectin-1- and IL-23-dependent manner. In summary, Dectin-1-dependent IL-17A production in the lungs during invasive fungal infection is mediated in part by CD11b(+) Ly-6G(+) neutrophils in an IL-23-dependent manner.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Aspergillus fumigatus / immunology
  • Aspergillus fumigatus / pathogenicity*
  • Cells, Cultured
  • Interleukin-17 / biosynthesis*
  • Interleukin-23 / deficiency
  • Interleukin-23 / genetics
  • Interleukin-23 / metabolism*
  • Lectins, C-Type
  • Lung / cytology
  • Lung / immunology
  • Lung / metabolism
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / deficiency
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neutrophils / immunology
  • Neutrophils / metabolism*
  • Pulmonary Aspergillosis / immunology*
  • Pulmonary Aspergillosis / microbiology

Substances

  • Interleukin-17
  • Interleukin-23
  • Lectins, C-Type
  • Membrane Proteins
  • Nerve Tissue Proteins
  • dectin 1