In Vitro Studies On The Role Of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) In Pulmonary Epithelial Cell Interactions To A. fumigatus.

N. Chaudhary, J. Staab, K. Marr

Author address: 

School of Medicine, Johns Hopkins University, Baltimore, MD.


RATIONALE: Aspergillus fumigatus, an opportunistic mold, colonizes the airways of up to 50% of cystic fibrosis (CF) patients. The most common complication of Aspergillus infection in CF patients is a destructive allergic response, allergic bronchopulmonary aspergillosis (ABPA). The significance of airway colonization of Aspergillus species is controversial; historically these organisms were considered as innocent saprophytes, however, our prior in vivo studies suggest that A. fumigatus hyphal antigens drive a TH-2 bias in CF models. This study was aimed to determine if CFTR mutations impact pulmonary epithelial cell responses to A. fumigatus. METHODS: Binding/uptake of Af293 conidia was evaluated using bronchial epithelial cell line with 916;F508/W1282X mutations, IB3 and corrected wild-type cell line, S9. Cytokines/chemokines were examined in Af293 conidia or germ-tube (GT)-stimulated S9 and IB3 cells. Effect of Af293 on cellular apoptosis/death was studied using AnnexinV/PI, M-30 and PARP-1 staining. RESULTS: Decreased binding and uptake (3-fold) of Af293 conidia was observed in IB3 cells than S9 cells. When compared to IB3 cells, GT-stimulated S9 cells secreted higher MCP-1 (2-fold), PGE-2 (15-fold) and IL-6(10-fold). PARP-1 and M-30 staining showed 10-fold and 4-fold higher apoptosis in Af293 conidia treated IB3 cells, respectively. CONCLUSIONS: A. fumigatus hyphal morphotypes, but not conidia, induce inflammatory mediators from epithelial cells. Epithelial cells harboring CFTR mutations bind and ingest less conidia, causing increased exposure to hyphal antigens, hence, different inflammatory responses; at least part of this is driven by enhanced apoptosis. These findings support that an inefficient airway clearance of A. fumigatus conidia allows exposure to inflammation-evoking hyphal antigens, driving ABPA.

abstract No: 


Full conference title: 

American Academy of Allergy Asthma & Immunology
    • AAAAI 2010 (66th)