Nonpathogenic, Environmental Fungi Induce Activation and Degranulation of Human Eosinophils

Abstract

Eosinophils and their products are probably important in the pathophysiology of allergic diseases, such as bronchial asthma, and in host immunity to certain organisms. An association between environmental fungal exposure and asthma has been long recognized clinically. Although products of microorganisms (e.g., lipopolysaccharides) directly activate certain inflammatory cells (e.g., macrophages), the mechanism(s) that triggers eosinophil degranulation is unknown. In this study we investigated whether human eosinophils have an innate immune response to certain fungal organisms. We incubated human eosinophils with extracts from seven environmental airborne fungi (Alternaria alternata, Aspergillus versicolor, Bipolaris sorokiniana, Candida albicans, Cladosporium herbarum, Curvularia spicifera, and Penicillium notatum). Alternaria and Penicillium induced calcium-dependent exocytosis (e.g., eosinophil-derived neurotoxin release) in eosinophils from normal individuals. Alternaria also strongly induced other activation events in eosinophils, including increases in intracellular calcium concentration, cell surface expression of CD63 and CD11b, and production of IL-8. Other fungi did not induce eosinophil degranulation, and Alternaria did not induce neutrophil activation, suggesting specificity for fungal species and cell type. The Alternaria-induced eosinophil degranulation was pertussis toxin sensitive and desensitized by preincubating cells with G protein-coupled receptor agonists, platelet-activating factor, or FMLP. The eosinophil-stimulating activity in Alternaria extract was highly heat labile and had an Mr of ∼60 kDa. Thus, eosinophils, but not neutrophils, possess G protein-dependent cellular activation machinery that directly responds to an Alternaria protein product(s). This innate response by eosinophils to certain environmental fungi may be important in host defense and in the exacerbation of inflammation in asthma and allergic diseases.

Eosinophils Contribute to IL-4 Production and Shape the T-Helper Cytokine Profile and Inflammatory Response in Pulmonary Cryptococcosis

“…71 In addition, antiviral effects have been reported. 72 Investigations of the role of eosinophils in fungal infection with Candida albicans, [73][74][75] Alternaria alternata, 76 or C. neoformans 10,23,41,42 were made, with a focus on their effector function. Similarly, a study 10 using anti-IL-5 treatment showed an association of eosinophil frequency with susceptibility during cryptococcosis.…”

Melanized Fungi in Human Disease

“…The virulence factors in these fungi that are responsible for eliciting allergic reactions are not well understood, though Alternaria was found to stimulate the degranulation of eosinophils, possibly due to an aspartic protease (372,496). These organisms are very common in the environment, so exposure is practically universal, though the incidence of allergic disease is relatively low, suggesting that host factors may play a role.…”

Distinct Endocytic Mechanisms of CD22 (Siglec-2) and Siglec-F Reflect Roles in Cell Signaling and Innate Immunity

“…In this regard, a recent report analyzing Siglec-F null mice revealed enhanced eosinophil infiltration and blood eosinophilia in response to allergen challenge, suggesting that Siglec-F is a negative regulator of eosinophil response to allergens (86). Eosinophils also contribute to an immune response against foreign pathogens, including binding, engulfment, and killing of microbes (1,15,19,32,36,83). While investigating the endocytic activity of Siglec-F, we observed efficient endocytosis of anti-Siglec antibody, high-affinity sialoside ligand probes, and Neisseria meningitidis bearing sialylated glycans.…”