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Infection and Immunity, October 2004, p. 6087-6094, Vol. 72, No. 10
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.10.6087-6094.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Modulation of Airway Inflammation by Immunostimulatory CpG Oligodeoxynucleotides in a Murine Model of Allergic Aspergillosis

Banani Banerjee,1* Kevin J. Kelly,1 Jordan N. Fink,1 James D. Henderson Jr.,2,3 Naveen K. Bansal,4 and Viswanath P. Kurup1,3

Allergy-Immunology Division, Department of Pediatrics,1 Department of Surgery Medical College of Wisconsin,2 Research Service, VA Medical Center,3 Department of Mathematics, Marquette University, Milwaukee, Wisconsin4

Received 19 December 2003/ Returned for modification 19 January 2004/ Accepted 16 June 2004

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.

* Corresponding author. Mailing address: VA Medical Center, Research Service 151-I, 5000 West National Ave., Milwaukee, WI 53295. Phone: (414) 384-2000, ext. 41510. Fax: (414) 382-5374. E-mail: banerjee{at}mcw.edu.

Editor: T. R. Kozel

Infection and Immunity, October 2004, p. 6087-6094, Vol. 72, No. 10
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.10.6087-6094.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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