RATIONALE: Aspergillus versicolor is a ubiquitous contaminant of damp indoor environments and common source of personal exposure in the United States. In this study, a subchronic exposure model was used to assess the immunological effects following repeated A. versicolor conidia challenge.
METHODS: Female B6C3F1/N mice were exposed to an average of 3.5x105 A. versicolor conidia or HEPA-filtered air twice per week for up to 13 weeks. Serum, bronchoalveolar lavage fluid (BALF), and lungs were collected 24 hours following the final exposure. Leukocytes derived from lung tissue were analyzed via flow cytometry. Serum and BALF cytokines were measured using multiplexed immunoassays.
RESULTS: Following 1 week of repeated exposure, innate cells, particularly alveolar macrophages, dendritic cells, and inflammatory monocytes were increased in lungs of conidia-exposed mice compared to air-only controls. Infiltration of innate cells, B- and T-cells, as well as type 2 innate lymphoid cells (ILC2s) were observed following 2 weeks exposure intervals. With the exception of ILC2s, cellular infiltration of innate and adaptive cells peaked following 4 weeks of repeated exposure. Serum and BALF cytokines including IL4, IL5, and IL13, were detected after 4 weeks. Cellular infiltration was decreased at 13 weeks for all cell types except ILC2s, which were increased. Concomitantly, IL4, CCL3 and CCL4 were also slightly increased in BALF of A. versicolor-exposed mice.
CONCLUSIONS: These data demonstrate a continuum of pulmonary immune responses following A. versicolor exposure initially characterized by a mixed Th1 and Th2 response that shifts to a Th2-dominant response by 13 weeks, with ILC2s and Th2 cytokines remaining elevated.
Full conference title:
- AAAAI 2019