Abstract
We have previously reported that compromised IL-17A production in the lungs increased susceptibility to infection with the invasive fungal pathogen Aspergillus fumigatus. Here, we show 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-1ß 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 WT and Dectin-1 deficient lung cells, although the addition of IL-6 or IL-1ß did not augment the effect of IL-23. Intracellular cytokine staining of lung cells revealed lower 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 demonstrate that Ly-6G+ neutrophils required the presence of myeloid cells for IL-17A production. Finally, upon in vitro stimulation with A. fumigatus, thioglycollate-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.
Original language | English |
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Pages (from-to) | 3966-3977 |
Number of pages | 12 |
Journal | Infection and Immunity |
Volume | 79 |
Issue number | 10 |
Early online date | 1 Aug 2011 |
DOIs | |
Publication status | Published - Oct 2011 |