title: Neutrophils produce interleukin 17A (IL-17A) in a dectin-1- and IL-23-dependent manner during invasive fungal infection.
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.
authors.affiliation: Department of Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Werner
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Gessner
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Lilly
authors.forename: Michael P
authors.initials: MP
authors.lastname: Nelson
authors.forename: Allison E
authors.initials: AE
authors.lastname: Metz
authors.forename: Dawn
authors.initials: D
authors.lastname: Horn
authors.forename: Chad W
authors.initials: CW
authors.lastname: Dunaway
authors.forename: Jessy
authors.initials: J
authors.lastname: Deshane
authors.forename: David D
authors.initials: DD
authors.lastname: Chaplin
authors.forename: Casey T
authors.initials: CT
authors.lastname: Weaver
authors.forename: Gordon D
authors.initials: GD
authors.lastname: Brown
authors.forename: Chad
authors.initials: C
authors.lastname: Steele
mesh_terms: D000818:Animals; D001232:Aspergillus fumigatus / Q000276:immunology / Q000472:pathogenicity*; D002478:Cells, Cultured; D020381:Interleukin-17 / Q000096:biosynthesis*; D053759:Interleukin-23 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D037181:Lectins, C-Type; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D055732:Pulmonary Aspergillosis / Q000276:immunology* / Q000382:microbiology; D000099181:Dectin-1
chemical_list: D020381:Interleukin-17; D053759:Interleukin-23; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D000099181:Dectin-1