Immunopathogenesis of allergic bronchopulmonary aspergillosis in cystic fibrosis.
Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease mediated by an allergic late-phase inflammatory response to Aspergillus fumigatus antigens. ABPA is characterized by markedly elevated Aspergillus-specific and total IgE levels and eosinophilia, and manifested by wheezing, pulmonary infiltrates, and bronchiectasis and fibrosis, which afflict asthmatic and cystic fibrosis (CF) patients. We propose that ABPA develops in genetically susceptible CF patients due to HLA-DR2 and DR5 restriction, increased sensitivity to IL-4 stimulation, and increased A. fumigatus allergen-specific Th2 CD4+ T-cell-mediated responses. In addition, A. fumigatus proteases play a role in facilitation of antigen transport across the epithelial cell layer by damaging the epithelial integrity and by a direct interaction with epithelial cell surface receptors, resulting in pro-inflammatory cytokine production and corresponding inflammatory responses.
Pediatric Research Institute, St. Louis University Health Sciences Center, 3662 Park Avenue, St. Louis, MO 63110, USA. knutsenm@slu.edu
Alan P
AP
Knutsen
Clifford
C
Bellone
Henk
H
Kauffman
D000908:Antibodies, Fungal / Q000276:immunology*; D000938:Antigen-Presenting Cells; D000946:Antigens, Fungal / Q000276:immunology*; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000276:immunology*; D001232:Aspergillus fumigatus; D003550:Cystic Fibrosis / Q000150:complications / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D006681:HLA-D Antigens / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D020545:Respiratory Mucosa / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000908:Antibodies, Fungal; D000946:Antigens, Fungal; D016207:Cytokines; D006681:HLA-D Antigens; D007073:Immunoglobulin E