Faculty Collaboration Database

Modulation of airway inflammation by immunostimulatory CpG oligodeoxynucleotides in a murine model of allergic aspergillosis. Infect Immun 2004 Oct;72(10):6087-94

Date

09/24/2004

Pubmed ID

15385513

Pubmed Central ID

PMC517601

DOI

10.1128/IAI.72.10.6087-6094.2004

Scopus ID

2-s2.0-4644258165 (requires institutional sign-in at Scopus site)   44 Citations

Abstract

Allergic aspergillosis is a Th2 T-lymphocyte-mediated pulmonary complication in patients with atopic asthma and cystic fibrosis. Therefore, any therapeutic strategy that selectively inhibits Th2 T-cell activation may be useful in downregulating allergic lung inflammation in asthma. In the present study, we developed a CpG oligodeoxynucleotide (ODN)-based immune intervention of allergic inflammation in a mouse model of allergic aspergillosis. Four different groups of mice were used in a short-term immunization protocol. Three experimental groups of animals (groups 1 to 3) were sensitized with Aspergillus fumigatus antigens. Animals in group 1 were immunized with A. fumigatus antigen alone, while those in group 2 were treated with CpG-ODN 1 day before the first antigen immunization, and the animals in group 3 received the first CpG-ODN administration between the antigen treatments. The animals in group 4 served as controls and were given phosphate-buffered saline. Allergen-specific serum immunoglobulins and total immunoglobulin E in different groups of animals were measured by enzyme-linked immunosorbent assay, while airway remodeling and cytokine production were studied by immunohistochemistry. The results demonstrated that CpG-ODN administration either before (group 2) or between (group 3) antigen treatments resulted in reduced total immunoglobulin E levels and peripheral blood eosinophil numbers compared to A. fumigatus allergen-sensitized group 1 animals. Similarly, treatment with CpG-ODN also downregulated inflammatory cell infiltration, goblet cell hyperplasia, and basement membrane thickening compared to A. fumigatus-sensitized mice. The distinct reduction in peripheral blood eosinophilia and airway remodeling in CpG-ODN-treated mice emphasized its usefulness as an immunomodulating agent for allergic fungal diseases.

Author List

Banerjee B, Kelly KJ, Fink JN, Henderson JD Jr, Bansal NK, Kurup VP

Author

Banani Banerjee PhD Associate Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Allergens
Animals
Antibodies, Fungal
Antigens, Fungal
Aspergillosis, Allergic Bronchopulmonary
Aspergillus fumigatus
Basement Membrane
Bronchoalveolar Lavage Fluid
CpG Islands
Disease Models, Animal
Down-Regulation
Eosinophilia
Eosinophils
Glycoproteins
Immunoglobulin E
Inflammation
Interleukin-4
Interleukin-5
Leukocyte Count
Lung
Mice
Mucous Membrane
Oligodeoxyribonucleotides