title: Aspergillus fumigatus generates an enhanced Th2-biased immune response in mice with defective cystic fibrosis transmembrane conductance regulator.
abstract: Cystic fibrosis (CF) lung disease is characterized by persistent airway inflammation and airway infection that ultimately leads to respiratory failure. Aspergillus sp. are present in the airways of 20-40% of CF patients and are of unclear clinical significance. In this study, we demonstrate that CF transmembrane conductance regulator (CFTR)-deficient (CFTR knockout, Cftr(tm1Unc-)TgN(fatty acid-binding protein)CFTR) and mutant (DeltaF508) mice develop profound lung inflammation in response to Aspergillus fumigatus hyphal Ag exposure. CFTR-deficient mice also develop an enhanced Th2 inflammatory response to A. fumigatus, characterized by elevated IL-4 in the lung and IgE and IgG1 in serum. In contrast, CFTR deficiency does not promote a Th1 immune response. Furthermore, we demonstrate that CD4+ T cells from naive CFTR-deficient mice produce higher levels of IL-4 in response to TCR ligation than wild-type CD4+ T cells. The Th2 bias of CD4+ T cells in the absence of functional CFTR correlates with elevated nuclear levels of NFAT. Thus, CFTR is important to maintain the Th1/Th2 balance in CD4+ T cells.
authors.affiliation: Vermont Lung Center, Division of Pulmonary Disease and Critical Care, Department of Medicine, University of Vermont, Burlington, VT 05405, USA.
authors.forename: Jenna B
authors.initials: JB
authors.lastname: Allard
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Poynter
authors.forename: Kieren A
authors.initials: KA
authors.lastname: Marr
authors.forename: Lauren
authors.initials: L
authors.lastname: Cohn
authors.forename: Mercedes
authors.initials: M
authors.lastname: Rincon
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Whittaker
mesh_terms: D000818:Animals; D000946:Antigens, Fungal / Q000276:immunology; D001232:Aspergillus fumigatus / Q000276:immunology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000172:deficiency* / Q000276:immunology*; D006706:Homeostasis / Q000276:immunology; D007109:Immunity; D007249:Inflammation; D008168:Lung / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000946:Antigens, Fungal; D019005:Cystic Fibrosis Transmembrane Conductance Regulator