Modulation of airway inflammation by immunostimulatory CpG oligodeoxynucleotides in a murine model of allergic aspergillosis.
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.
Banerjee
Banani
B
Allergy-Immunology Division, Department of Pediatrics, Medical College of Wisconsin, Research Service, VA Medical Center, Milwaukee, Wisconsin 53295, USA. banerjee@mcw.edu
Kelly
Kevin J
KJ
Fink
Jordan N
JN
Henderson
James D
JD
Bansal
Naveen K
NK
Kurup
Viswanath P
VP
D000485:Allergens / Q000276:immunology; D000818:Animals; D000908:Antibodies, Fungal / Q000097:blood / Q000276:immunology; D000946:Antigens, Fungal / Q000276:immunology; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D001232:Aspergillus fumigatus / Q000276:immunology; D001485:Basement Membrane / Q000187:drug effects / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D018899:CpG Islands / Q000235:genetics; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D004802:Eosinophilia / Q000188:drug therapy / Q000473:pathology; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects; D006023:Glycoproteins / Q000096:biosynthesis; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology* / Q000627:therapeutic use
D000485:Allergens; D000908:Antibodies, Fungal; D000946:Antigens, Fungal; C408982:CPG-oligonucleotide; D006023:Glycoproteins; D015848:Interleukin-5; D009838:Oligodeoxyribonucleotides; D015847:Interleukin-4; D007073:Immunoglobulin E