Background: Pulmonary exposure to Aspergillus fumigatus has been associated with respiratory morbidity and mortality. A. fumigatus produces viable thermotolerant conidia that secrete proteases and other immunostimulatory factors upon germination. Murine models have shown the thermotolerant phenotype is important in the initiation of invasive disease. To date, the cellular immune response to the thermotolerant A. fumigatus, in comparison to other non-thermotolerant Aspergillus species such as A. versicolor, remains uncharacterized. Methods: BALB/c mice were exposed by aspiration to 106 conidia of A. fumigatus or A. versicolor twice a week for two weeks. After a two-week recovery period, mice were given a final conidia challenge. Three days after the final aspiration, mice were sacrificed, and bronchoalveolar lavage fluid (BALF) was collected and analyzed by flow cytometry. Cellular composition and conidial clearance were examined. A fraction of the BALF cells were stimulated with PMA/Ionomycin and stained for intracellular cytokine production. Results: Mice that aspirated A. fumigatus or A. versicolor conidia exhibited similar airway inflammation that was characterized by infiltration of neutrophils, eosinophils, and T lymphocytes. BALF T cells isolated from A. fumigatus exposed mice produced IFN-γ , whereas the T-cell response to A. versicolor was characterized by IL-4 production. Activated IFN-γ -producing CD8+ T cells were isolated from the BALF of mice that aspirated A. fumigatus, with the number of cells increased eight-fold when compared to the BALF of A. versicolor-challenged mice. Mice that had previously aspirated A. fumigatus conidia more efficiently cleared conidia in comparison to a delayed clearance in the airways of naí¯ve mice. Conclusions: Murine BALF cellular immune responses to Aspergillus conidia may be fungal species-dependent and may enhance alveolar clearance of conidia. Furthermore, differences in the response to challenges of specific species may depend on thermotolerance.
Full conference title:
110th General Meeting American Society for Microbiology
- ASM 110th (2010)