Comparison of Proteomic Profiles Influencing Pulmonary Immune Responses Following Repeated Exposure to Aspergillus and Stachybotrys species

Tara L. Croston, PhD1 , Mark A. Barnes, Jr, PhD1 , Angela R. Lemons, MS1 , Ajay P. Nayak, PhD1 , Dori Germolec, PhD2 , Donald H. Beezhold, PhD FAAAAI1 , and Brett J. Green, PhD FAAAAI1

Author address: 

1 Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV, 2 Toxicology Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC

Abstract: 

RATIONALE: Adverse respiratory health effects have been associated with damp indoor environments and fungal contamination. Comparing molecular profiles following fungal exposures may help identify new biomarkers of fungal exposure.

METHODS: Mice repeatedly inhaled one of three fungal species: Aspergillus fumigatus (1x105 conidia), Aspergillus versicolor (3.5x105 conidia), Stachybotrys chartarum (1x104 conidia), or air (AOC) twice a week for 13 weeks. Murine lungs harvested 24 hours post-exposure were homogenized and processed for proteomic and RNA analyses. Molecular pathways were analyzed utilizing Qiagen’s Ingenuity Pathway Analysis software.

RESULTS: Proteomic analysis revealed that following S. chartarum exposure, 29% of the 3,915 detected proteins were differentially expressed compared to AOC; whereas 13% of 3,176 proteins were altered after A. versicolor exposure and 7% of 2,152 proteins were altered following A. fumigatus(7%) exposure. Comparative analysis identified 11 proteins that were in common with all 3 fungal exposures, including ARHGDIB and COTL1, known to be involved in tissue morphology and antifungal defense, respectively. Additional associations were identified with neurological and immunological disease, and with inflammatory responses. The Aspergillus species shared only 4 proteins, whereas S. chartarum shared 10-fold more proteins with each Aspergillus species. Also involved in immunological disease, IPA predicted that 27 miRNAs, common to all 3 fungal exposures, regulated the 11 identified proteins.

CONCLUSIONS: While exposure to individual fungal species influences multiple host response mechanisms, common proteins could be identified to serve as potential biomarkers for fungal exposure. These results identified additional proteins and miRNAs in fungal exposure that have not been previously reported.

2019

abstract No: 

564

Full conference title: 

American Academy of Allergy, Asthma & Immunology 2019
    • AAAAI 2019