title: Evolution of the Immune Response to Chronic Airway Colonization with Aspergillus fumigatus Hyphae.
abstract: Airway colonization by the mold Aspergillus fumigatus is common in patients with underlying lung disease and is associated with chronic airway inflammation. Studies probing the inflammatory response to colonization with A. fumigatus hyphae have been hampered by the lack of a model of chronic colonization in immunocompetent mice. By infecting mice intratracheally with conidia embedded in agar beads (Af beads), we have established an in vivo model to study the natural history of airway colonization with live A. fumigatus hyphae. Histopathological examination and galactomannan assay of lung homogenates demonstrated that hyphae exited beads and persisted in the lungs of mice up to 28 days postinfection without invasive disease. Fungal lesions within the airways were surrounded by a robust neutrophilic inflammatory reaction and peribronchial infiltration of lymphocytes. Whole-lung cytokine analysis from Af bead-infected mice revealed an increase in proinflammatory cytokines and chemokines early in infection. Evidence of a Th2 type response was observed only early in the course of colonization, including increased levels of interleukin-4 (IL-4), elevated IgE levels in serum, and a mild increase in airway responsiveness. Pulmonary T cell subset analysis during infection mirrored these results with an initial transient increase in IL-4-producing CD4(+) T cells, followed by a rise in IL-17 and Foxp3(+) cells by day 14. These results provide the first report of the evolution of the immune response to A. fumigatus hyphal colonization.
authors.affiliation: Department of Microbiology and Immunology, McGill University, Montréal, Québec, Canada.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Urb
authors.affiliation: Department of Microbiology and Immunology, McGill University, Montréal, Québec, Canada.
authors.forename: Brendan D
authors.initials: BD
authors.lastname: Snarr
authors.affiliation: Department of Human Genetics, McGill University, Montréal, Québec, Canada.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Wojewodka
authors.affiliation: Department of Microbiology and Immunology, McGill University, Montréal, Québec, Canada.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Lehoux
authors.affiliation: Department of Microbiology and Immunology, McGill University, Montréal, Québec, Canada.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Immunology, McGill University, Montréal, Québec, Canada.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ralph
authors.affiliation: Department of Microbiology and Immunology, McGill University, Montréal, Québec, Canada Department of Medicine, McGill University, Montréal, Québec, Canada Meakins-Christie Laboratories, McGill University, Montréal, Québec, Canada Department of Pathology, McGill University, Montréal, Québec, Canada McGill University Health Centre, McGill University, Montréal, Québec, Canada McGill International TB Centre, McGill University, Montréal, Québec, Canada Centre for Translational Biology, McGill University, Montréal, Québec, Canada.
authors.forename: Maziar
authors.initials: M
authors.lastname: Divangahi
authors.affiliation: Department of Microbiology and Immunology, McGill University, Montréal, Québec, Canada.
authors.forename: Irah L
authors.initials: IL
authors.lastname: King
authors.affiliation: Department of Medicine, McGill University, Montréal, Québec, Canada Meakins-Christie Laboratories, McGill University, Montréal, Québec, Canada.
authors.forename: Toby K
authors.initials: TK
authors.lastname: McGovern
authors.affiliation: Department of Medicine, McGill University, Montréal, Québec, Canada Meakins-Christie Laboratories, McGill University, Montréal, Québec, Canada.
authors.forename: James G
authors.initials: JG
authors.lastname: Martin
authors.affiliation: Department of Pathology, McGill University, Montréal, Québec, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Fraser
authors.affiliation: Department of Human Genetics, McGill University, Montréal, Québec, Canada.
authors.forename: Danuta
authors.initials: D
authors.lastname: Radzioch
authors.affiliation: Department of Microbiology and Immunology, McGill University, Montréal, Québec, Canada Department of Medicine, McGill University, Montréal, Québec, Canada donald.sheppard@mcgill.ca.
authors.forename: Donald C
authors.initials: DC
authors.lastname: Sheppard
mesh_terms: D000818:Animals; D001232:Aspergillus fumigatus / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D025301:Hyphae / Q000276:immunology*; D016130:Immunophenotyping; D051379:Mice; D008810:Mice, Inbred C57BL; D055732:Pulmonary Aspergillosis / Q000276:immunology* / Q000473:pathology*; D016176:T-Lymphocyte Subsets / Q000276:immunology