Aspergillus fumigatusInduces Immunoglobulin E–Independent Mast Cell Degranulation

Abstract

Pulmonary colonization by Aspergillus fumigatus in chronic lung disease is associated with progressive decline in lung function even in the absence of specific allergic response. We hypothesized that A. fumigatus contributes to this decline by inducing pulmonary mast cell degranulation even in the absence of antigen-specific immunoglobulin E (IgE). Therefore, we investigated whether A. fumigatus can induce mast cell degranulation independently of IgE. We studied the interactions of Aspergillus species with mast cells in the absence of IgE in vitro with use of scanning electron microscopy. The extent of mast cell degranulation was quantified by measuring the release of beta-hexosaminidase. Mature A. fumigatus hyphae induced mast cell degranulation in the absence of IgE. Hyphae of Aspergillus flavus, Aspergillus niger, and Aspergillus nidulans induced much less mast cell degranulation. Mast cell degranulation required direct contact with mature A. fumigatus hyphae, and was not induced by conidia or immature hyphae. Killed hyphae induced significant degranulation, whereas live hyphae from mutants deficient in the fungal development regulators StuA and MedA induced very little degranulation. Factors expressed on the surface of mature A. fumigatus hyphae that are controlled by StuA and MedA induce mast cell degranulation in the absence of IgE.