Mold Inhalation Modulates Innate Immune Cells in the Lungs

Aspergillus fumigatus is a ubiquitously present fungal pathogen and household mold. While inhalation of A. fumigatus in immunocompetent individuals can be associated with increased host susceptibility to infections and allergy, the mechanisms underlying these effects are unknown. Interestingly, exposure to the fungal vaccine adjuvant ꞵ-glucan epigenetically reprograms hematopoietic stem and progenitor cells (HSPCs) and thereby enhances host resistance to infection, mediated through “improved” innate immune cells. We hypothesize that A. fumigatus exposure, in contrast to ꞵ-glucan, maladaptively reprograms HSPCs, resulting in an impaired innate immune response to subsequent stimuli. To investigate this hypothesis, we intranasally administered a subclinical dose of A. fumigatus allergen (AFA) or saline to C57BL/6 mice. On days 7 and 30 post exposure, quantitative alterations in lung immune cell and bone marrow HSPC populations were characterized by flow cytometry. To determine the functional implication of mold inhalation on myeloid cells, bone marrow-derived macrophages were generated from the bone marrow cells of saline- and AFA-exposed mice. Interestingly, we found long-term elevated levels of granulopoietic and myeloid cell populations in the lung after AFA exposure. However, the functional repertoire of macrophages remained unchanged, suggesting that quantitative, rather than qualitative changes mediate the long-term effects of AFA exposure. Mold exposure occurs in up to 40% of Canadian houses. Determining the pathophysiology of mold exposure in immunocompetent individuals will allow for development of targeted treatments to alleviate long-term detrimental consequences.