Enhanced IgE allergic response to Aspergillus fumigatus in CFTR-/- mice.
To gain insight into aberrant cytokine regulation in cystic fibrosis (CF), we compared the phenotypic manifestations of allergen challenge in gut-corrected CFTR-deficient mice with background-matched C57Bl6 (B6) mice. Aspergillus fumigatus (Af) antigen was used to mimic allergic bronchopulmonary aspergillosis, a peculiar hyper-IgE syndrome with a high prevalence in CF patients. CFTR-/-, C57BL/6 and FVB/NJ mice were sensitized with Af antigen by serial intraperitoneal injections. Control mice were mock sensitized with PBS. Challenges were performed by inhalation of Af antigen aerosol. After Af antigen challenge, histologic analysis showed goblet cell hyperplasia and lymphocytic infiltration in both strains. However, total serum IgE levels were markedly elevated in CF mice. Sensitized CF mice showed a five-fold greater IgE response to sensitization as compared with B6- and FVB-sensitized controls. Additional littermate controls to fully normalize for B6-FVB admixture in the strain background confirmed the role of CFTR mutation in the hyper-IgE syndrome. Cytokine mRNA levels of IL-5 and GM-CSF in the bronchoalveolar lavage (BAL) fluid, and BAL cell differentials indicated that CFTR mutation caused a shift from an IL-5-predominant to an IL-4-predominant cytokine profile. This system models a very specific type of airway inflammation in CF and could provide insights into pathogenesis and treatment of the disease.
Müller
Christian
C
Department of Pediatrics, Center for Immunology and Transplantation and Genetics Institute, University of Florida College of Medicine, Gainesville, FL 32610-0296, USA.
Braag
Sofia A
SA
Herlihy
John-David
JD
Wasserfall
Clive H
CH
Chesrown
Sarah E
SE
Nick
Harry S
HS
Atkinson
Mark A
MA
Flotte
Terence R
TR
D000485:Allergens / Q000276:immunology; D000818:Animals; D001232:Aspergillus fumigatus / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction
D000485:Allergens; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D007073:Immunoglobulin E