A Deletion Variant of the Aspergillus fumigatus Ribotoxin Asp f 1 Induces an Attenuated Airway Inflammatory Response in a Mouse Model of Sensitization

Abstract

α-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. α-Sarcin Δ(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 α-sarcin Δ(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 α-sarcin Δ(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 purifi ed protein was fi rst 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 confi rming in vivo its lower toxic character. Conclusions: An easily reproducible mouse model of A fumigatus Asp f 1 sensitization was established. This model revealed α-sarcin Δ (7-22) to be a potential candidate for immunotherapy.