Influence of Aspergillus fumigatus conidia viability on murine pulmonary microRNA and mRNA expression following subchronic inhalation exposure

Details

• Personal Author:
  Beezhold, Donald H. ; Croston TL ; Germolec DR ; Goldsmith WT ; Green, Brett J. ; Gu JK ; Lemons, Angela R. ; Nayak, Ajay P.
• Description:
  Background: Personal exposure to fungal bioaerosols derived from contaminated building materials or agricultural commodities may induce or exacerbate a variety of adverse health effects. The genomic mechanisms that underlie pulmonary immune responses to fungal bioaerosols have remained unclear. Objective: The impact of fungal viability on the pulmonary microRNA and messenger RNA profiles that regulate murine immune responses was evaluated following subchronic inhalation exposure to Aspergillus fumigatus conidia. Methods: Three groups of naïve B6C3F1/N mice were exposed via nose-only inhalation to A. fumigatus viable conidia, heat-inactivated conidia, or HEPA-filtered air twice a week for 13 weeks. Total RNA was isolated from whole lung 24 and 48 hours post final exposure and was further processed for gene expression and microRNA array analysis. The molecular network pathways between viable and heat-inactivated conidia groups were evaluated. Results: Comparison of datasets revealed increased Il4, Il13, and Il33 expression in mice exposed to viable versus heat-inactivated conidia. Of 415 microRNAs detected, approximately 50% were altered in mice exposed to viable versus heat-inactivated conidia 48 hours post exposure. Significantly downregulated (P ≤ 0.05) miR-29a-3p was predicted to regulate TGF-β 3 and Clec7a, genes involved in innate responses to viable A. fumigatus. Also significantly downregulated (P ≤ 0.05), miR-23b-3p regulates genes involved in pulmonary IL-13 and IL-33 responses and SMAD2, downstream of TGF-β signaling. Using Ingenuity Pathway Analysis, a novel interaction was identified between viable conidia and SMAD2/3. Conclusion and Clinical Relevance: Examination of the pulmonary genetic profiles revealed differentially expressed genes and microRNAs following subchronic inhalation exposure to A. fumigatus. MicroRNAs regulating genes involved in the pulmonary immune responses were those with the greatest fold change. Specifically, germinating A. fumigatus conidia were associated with Clec7a and were predicted to interact with Il13 and Il33. Furthermore, altered microRNAs may serve as potential biomarkers to evaluate fungal exposure. [Description provided by NIOSH]
• Subjects:
  Biomarkers Fungi Genetics Hypersensitivity Immune System Laboratories Lung Occupational Health Respiratory System Safety
• Keywords:
  Allergens Animal Models Aspergillus Infection Author Keywords: Allergens And Epitopes Bioaerosols Immune Reaction Inhalation Laboratory Animals Pulmonary System
• ISSN:
  0954-7894
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  North Carolina ; OSHA Region 3 ; OSHA Region 4 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  46
• Issue:
  10
• NIOSHTIC Number:
  nn:20048603
• Citation:
  Clin Exp Allergy 2016 Oct; 46(10):1315-1327
• Contact Point Address:
  Tara L. Croston, Ph.D., Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, 1095 Willowdale Road, Morgantown, WV 26505
• Email:
  xzu9@cdc.gov
• Federal Fiscal Year:
  2017
• NORA Priority Area:
  Healthcare and Social Assistance ; Services
• Peer Reviewed:
  True
• Source Full Name:
  Clinical and Experimental Allergy
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:751a6519e7487c3e725dc5840f3c0a5adcc4363373c446fb785aeddd287b9d47ba938927b7cde3ef795280e1a0f0d47065dab44cdda5dfae787e70ceb061b5af
• Download URL:
  https://stacks.cdc.gov/view/cdc/203322/cdc_203322_DS1.pdf
• File Type:
  [PDF - 1.19 MB ]