RGD Reference Report - Neutrophils produce interleukin 17A (IL-17A) in a dectin-1- and IL-23-dependent manner during invasive fungal infection. - Rat Genome Database

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

Authors: Werner, JL  Gessner, MA  Lilly, LM  Nelson, MP  Metz, AE  Horn, D  Dunaway, CW  Deshane, J  Chaplin, DD  Weaver, CT  Brown, GD  Steele, C 
Citation: Werner JL, etal., Infect Immun. 2011 Oct;79(10):3966-77. doi: 10.1128/IAI.05493-11. Epub 2011 Aug 1.
RGD ID: 8698654
Pubmed: (View Article at PubMed) PMID:21807912
DOI: Full-text: DOI:10.1128/IAI.05493-11

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-1beta, 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-1beta 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.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Il17a  (interleukin 17A)

Genes (Mus musculus)
Il17a  (interleukin 17A)

Genes (Homo sapiens)
IL17A  (interleukin 17A)


Additional Information