Abstract
Occupational mold exposure can lead to Aspergillus-associated allergic diseases including asthma and hypersensitivity pneumonitis. Elevated IL-17 levels or disbalanced T-helper (Th) cell expansion were previously linked to Aspergillus-associated allergic diseases, whereas alterations to the Th cell repertoire in healthy occupationally exposed subjects are scarcely studied. Therefore, we employed functional immunoassays to compare Th cell responses to A. fumigatus antigens in organic farmers, a cohort frequently exposed to environmental molds, and non-occupationally exposed controls. Organic farmers harbored significantly higher A. fumigatus-specific Th-cell frequencies than controls, with comparable expansion of Th1- and Th2-cell frequencies but only slightly elevated Th17-cell frequencies. Accordingly, Aspergillus antigen-induced Th1 and Th2 cytokine levels were strongly elevated, whereas induction of IL-17A was minimal. Additionally, increased levels of some innate immune cell-derived cytokines were found in samples from organic farmers. Antigen-induced cytokine release combined with Aspergillus-specific Th-cell frequencies resulted in high classification accuracy between organic farmers and controls. Aspf22, CatB, and CipC elicited the strongest differences in Th1 and Th2 responses between the two cohorts, suggesting these antigens as potential candidates for future bio-effect monitoring approaches. Overall, we found that occupationally exposed agricultural workers display a largely balanced co-expansion of Th1 and Th2 immunity with only minor changes in Th17 responses.
Highlights
Humans inhale hundreds of airborne spores of environmental molds daily such as Aspergillus species [1]
When assessing effector and memory phenotypes of A. fumigatus-specific Th cells by CCR7 and CD45RA expression, no significant differences in relative distributions of phenotypes were found between organic farmers and controls (Figure 1b)
Not the focus of this study, we found that A. fumigatus mycelial lysate (AfuLy)-stimulated WB samples from organic farmers produced 10-fold greater levels of the Treg signature cytokine IL-10 than those from controls, while IL-10 release was strongly correlated with elevated Th1 and Th2 responses
Summary
Humans inhale hundreds of airborne spores of environmental molds daily such as Aspergillus species [1]. While healthy individuals can efficiently clear fungal spores from their lungs, chronic mold exposure is a major risk factor for the development of hypersensitivity. We and others have previously shown that environmental exposure to molds and mycotoxins can result in assayable alterations to the human mold-reactive T-cell repertoire and proinflammatory cytokine release [9,10,11]. These studies have been performed in predominantly residentially exposed subjects who had a relatively low risk of Aspergillus-associated diseases, whereas data regarding the specific impact of occupational mold exposure on Aspergillus fumigatus-antigen reactive T-cell expansion, polarization, and cytokine responses are scarce
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