Immune response to n-terminal and c-terminal deletion mutants of Aspergillus fumigatus major allergen ASP F 3 |
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| Authors: | Bhanu P Singh Banani Banerjee Puspanita Naik Jordan N Fink Viswanath P Kurup |
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| Institution: | (1) Allergy-Immunology Division, Department of Pediatrics, Medical College of Wisconsin, 8701 Watertown Plank Road, 53226 Milwaukee, WI;(2) VA Medical Center, Research Service 151-1, 5000 West National Avenue, 53295 Milwaukee, WI, USA;(3) Allergy and Immunology Section, Institute of Genomics and Integrative Biology, Delhi University Campus, Mall Road, 110007 Delhi, India |
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| Abstract: | The ubiquitous fungus Aspergillus fumigatus causes allergic rhinitis, asthma, sinusitis and allergic bronchopulmonary aspergillosis.
A number of major allergens from A. fumigatus are purified, but their structure-function role in the pathogenesis of disease
is not known. Such information is essential for devising alternative therapy of fungal allergic diseases. In the present study,
N-terminal and C-terminal deletion mutants ofAsp f 3 were constructed and their immunopathological responses studied in a mice model of allergy. Three mutants viz,Asp f 3 (aa 33–168), (aa 1–142), and (aa 23–142) were made by deleting certain amino acids from epitopic regions of full lengthAsp f 3, a major allergen of A. furnigatus. TheAsp f 3 and three mutated proteins were expressed in pET vector. The C-terminal deletion mutantAsp f 3 (aa 1–142) induced elevated IFN-γ but low levels of IL-4 by spleen cells. This mutant also showed significant downregulation
of peripheral blood eosinophils and lung inflammation in immunized mice. The N-terminal deletion mutantAsp f 3 (aa 33–168) also exhibited an immuno-suppressive effect in terms of IgE production and induction of Th2 cytokine. The results
indicate thatrAsp f 3 and its deletion mutants induced distinct immune-inflammatory responses in mice on challenge with these proteins. The non-IgE
binding deletion mutants ofAsp f 3 (aa 1–142 and aa 33–168) could deviate Th2 immune response with a concomitant reduction in airway inflammation and infiltration
of inflammatory cells. |
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| Keywords: | Aspergillus fumigatus rAsp f 3 Deletion mutants Murine model ABPA |
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