A deletion variant of the Aspergillus fumigatus ribotoxin Asp f 1 induces an attenuated airway inflammatory response in a mouse model of sensitization.

BACKGROUND Aspergillus fumigatus is the most prevalent airborne fungal pathogen, and the ribotoxin Asp f 1 is one of its major allergens. Alpha-Sarcin is a natural variant of Asp f 1 produced by the nonpathogenic fungus Aspergillus giganteus. Both proteins show a sequence identity of 87% and almost identical 3-dimensional structures. Alpha-Sarcin delta(7-22) is a deletion mutant that displays reduced immunoglobulin (Ig) E reactivity and is much less cytotoxic than wild-type proteins against human transformed cells. OBJECTIVE A murine model of sensitization to Asp f 1 was established to test the response elicited by this alpha-sarcin delta(7-22) deletion mutant. METHODS BALB/c mice were treated intraperitoneally with different mixtures of recombinant wild-type Asp f 1 and/or a suspension of a commercially available A. fumigatus standard extract. Mice were then intranasally challenged with Asp f 1 or alpha-sarcin delta(7-22). Sera were collected for subsequent measurement of Ig levels and histological analysis of the nostrils and lungs. RESULTS Sensitization to Asp f 1 was successful only when the purified protein was first administered together with the A fumigatus suspension. The model was characterized by elevated levels of total IgE in serum and histological lesions in the lungs and nostrils. These symptoms were less severe when the deletion variant was the protein administered, thus confirming in vivo its lower toxic character. CONCLUSIONS An easily reproducible mouse model of A fumigatus Asp f 1 sensitization was established. This model revealed alpha-sarcin delta(7-22) to be a potential candidate for immunotherapy.