Investigating local and systemic immune changes following sub-chronic inhalation of Aspergillus versicolor spores

Abstract

Abstract Fungi are environmentally ubiquitous, and can be particularly abundant in damp indoor locations which may lead to pulmonary fungal exposure via inhalation of bioaerosols. Some of the adverse pulmonary health effects associated with fungal challenges include asthma, allergy, hypersensitivity pneumonitis, and local or disseminated infection. Here, we study the innate immune effects following 13 weeks sub-chronic inhalation exposures to spores derived from a common indoor fungal contaminant, Aspergillus versicolor. Compared to air-only control mice, A. versicolor-exposed B6C3F1 mice exhibited increased recruitment of leukocytes to the lung, particularly eosinophils and type 2 innate lymphoid cells (ILC2s), but also alveolar macrophages, inflammatory monocytes, and neutrophils following 13 weeks of exposure in nose-only inhalation chambers. Local expression of ccl2, ccl7, eotaxin, and il13 mRNA was increased in lung tissue. In addition, IL-4, CCL3, CCL4, CXCL1, and CXCL5 were increased in bronchoaveolar lavage fluid of A. versicolor-exposed mice compared to controls. Systemically, circulating CCL7, CXCL1, CXCL5, and CXCL10 were increased in serum of mice following inhalation of spores. Taken together, these data indicate A. versicolor elicits a Th2-biased immune response that is driven by multiple innate immune cell populations, including monocytes, eosinophils, and ILC2s.