Pulmonary immune responses to Aspergillus fumigatus in an immunocompetent mouse model of repeated exposures.
Buskirk-AD; Templeton-SP; Nayak-AP; Hettick-JM; Law-BF; Green-BJ; Beezhold-DH
J Immunotoxicol 2014 Apr-Jun; 11(2):180-189
Aspergillus fumigatus is a filamentous fungus that produces abundant pigmented conidia. Several fungal components have been identified as virulence factors, including melanin; however, the impact of these factors in a repeated exposure model resembling natural environmental exposures remains unknown. This study examined the role of fungal melanin in the stimulation of pulmonary immune responses using immunocompetent BALB/c mice in a multiple exposure model. It compared conidia from wild-type A. fumigatus to two melanin mutants of the same strain, Delta arp2 (tan) or Delta alb1 (white). Mass spectrometry-based analysis of conidial extracts demonstrated that there was little difference in the protein fingerprint profiles between the three strains. Field emission scanning electron microscopy demonstrated that the immunologically inert Rodlet A layer remained intact in melanin-deficient conidia. Thus, the primary difference between the strains was the extent of melanization. Histopathology indicated that each A. fumigatus strain induced lung inflammation, regardless of the extent of melanization. In mice exposed to Delta alb1 conidia, an increase in airway eosinophils and a decrease in neutrophils and CD8+ IL-17+ (Tc17) cells were observed. Additionally, it was shown that melanin mutant conidia were more rapidly cleared from the lungs than wild-type conidia. These data suggest that the presence of fungal melanin may modulate the pulmonary immune response in a mouse model of repeated exposures to A. fumigatus conidia.
Respiratory-irritants; Pulmonary-function; Pulmonary-system; Lung-irritants; Fungi; Immune-reaction; Immunotoxins; Laboratory-animals; Laboratory-testing; Pigmentation; Pigments; Exposure-assessment; Exposure-methods; Analytical-models; Mass-spectrometry; Microscopic-analysis; Proteins; Histopathology; Neutrophils; Microorganisms; Polymers; Cell-function; Cellular-reactions;
Author Keywords: Aspergillus fumigatus; immune response; melanin; Tc17 cells
Donald H. Beezhold, PhD, Allergy and Clinical Immunology Branch, 1095 Willowdale Road. National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV 26505, USA
Healthcare and Social Assistance; Services
Journal of Immunotoxicology