title: Interleukin-17 drives pulmonary eosinophilia following repeated exposure to Aspergillus fumigatus conidia.
abstract: Previous research in our laboratory has demonstrated that repeated intranasal exposure to Aspergillus fumigatus conidia in C57BL/6 mice results in a chronic pulmonary inflammatory response that reaches its maximal level after four challenges. The inflammatory response is characterized by eosinophilia, goblet cell metaplasia, and T helper T(H)2 cytokine production, which is accompanied by sustained interleukin-17 (IL-17) expression that persists even after the T(H)2 response has begun to resolve. T(H)17 cells could develop in mice deficient in gamma interferon (IFN-γ), IL-4, or IL-10. In the lungs of IL-17 knockout mice repeatedly challenged with A. fumigatus conidia, inflammation was attenuated (with the most significant decrease occurring in eosinophils), conidial clearance was enhanced, and the early transient peak of CD4(+) CD25(+) FoxP3(+) cells blunted. IL-17 appeared to play only a minor role in eosinophil differentiation in the bone marrow but a central role in eosinophil extravasation from the blood into the lungs. These observations point to an expanded role for IL-17 in driving T(H)2-type inflammation to repeated inhalation of fungal conidia.
authors.affiliation: Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Murdock
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Falkowski
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Shreiner
authors.forename: Amir A
authors.initials: AA
authors.lastname: Sadighi Akha
authors.forename: Roderick A
authors.initials: RA
authors.lastname: McDonald
authors.forename: Eric S
authors.initials: ES
authors.lastname: White
authors.forename: Galen B
authors.initials: GB
authors.lastname: Toews
authors.forename: Gary B
authors.initials: GB
authors.lastname: Huffnagle
mesh_terms: D000818:Animals; D001232:Aspergillus fumigatus / Q000276:immunology* / Q000472:pathogenicity*; D015704:CD4 Antigens / Q000096:biosynthesis; D004804:Eosinophils / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D015847:Interleukin-4 / Q000276:immunology; D008168:Lung / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011014:Pneumonia; D055732:Pulmonary Aspergillosis / Q000276:immunology*; D011657:Pulmonary Eosinophilia / Q000276:immunology*; D013172:Spores, Fungal / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma