Title

Enhanced IgE allergic response to Aspergillus fumigatus in CFTR-/- mice

UMMS Affiliation

Gene Therapy Center; Department of Pediatrics

Date

2-21-2006

Document Type

Article

Medical Subject Headings

Aspergillus fumigatus; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Enzyme-Linked Immunosorbent Assay; Immunoglobulin E

Disciplines

Allergy and Immunology | Pediatrics | Respiratory Tract Diseases

Abstract

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.

Comments

Christian Mueller is cited on this publication as Christian Müller. At the time of publication, Christian Mueller, Sofia Braag, and Terence Flotte were not yet affiliated with the University of Massachusetts Medical School.

Citation: Lab Invest. 2006 Feb;86(2):130-40.

Related Resources

Link to Article in PubMed