Effect of Epithelial-Specific MyD88 Signaling Pathway on Airway Inflammatory Response to Organic Dust Exposure

Details

• Personal Author:
  Dickinson J ; Evans SE ; Gaurav R ; Janike K ; Johnson AN ; Kudrna K ; Nelson A ; Poole JA ; Wyatt TA
• Description:
  The Toll-like receptor (TLR) adaptor protein MyD88 is integral to airway inflammatory response to microbial-enriched organic dust extract (ODE) exposures. ODE-induced airway neutrophil influx and release of pro-inflammatory cytokines was essentially abrogated in global MyD88-deficient mice, yet these mice demonstrate an increase in airway epithelial cell mucin expression. To further elucidate the role of MyD88-dependent responses specific to lung airway epithelial cells in response to ODE in vivo, the surfactant protein C protein (SPC) Cre+ embryologic expressing airway epithelial cells floxed for MyD88 to disrupt MyD88 signaling were utilized. The inducible club cell secretory protein (CCSP) Cre+, MyD88 floxed, were also developed. Using an established protocol, mice were intranasally instilled with ODE or saline once or daily up to 3 weeks. Mice with MyD88-deficient SPC+ lung epithelial cells exhibited decreased neutrophil influx following ODE exposure once and repetitively for 1 week without modulation of classic pro-inflammatory mediators including tumor necrosis factor (TNF)-a, interleukin (IL)-6, and neutrophil chemoattractants. This protective response was lost after 3 weeks of repetitive exposure. ODE-induced Muc5ac mucin expression at 1 week was also reduced in MyD88-deficient SPC+ cells. Acute ODE-induced IL-33 was reduced in MyD88-deficient SPC+ cells whereas serum IgE levels were increased at one week. In contrast, mice with inducible MyD88-deficient CCSP+ airway epithelial cells demonstrated no significant difference in experimental indices following ODE exposure. Collectively, these findings suggest that MyD88-dependent signaling targeted to all airway epithelial cells plays an important role in mediating neutrophil influx and mucin production in response to acute organic dust exposures. [Description provided by NIOSH]
• Subjects:
  Agriculture Animals Dust Immune System Lung Diseases Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Adaptation Agricultural Industry Agriculture Airway Inflammation Animal Studies Author Keywords: Environmental Respiratory Disease Immune Reaction Lung Disease MyD88 Neutrophils Occupational Organic Dust Organic Dusts Respiratory Diseases

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• ISSN:
  1547-691X
• Document Type:
  Text
• Funding:
  Cooperative Agreement ; Grant
• Genre:
  Journal Article
• Place as Subject:
  Nebraska ; OSHA Region 6 ; OSHA Region 7 ; Texas
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  20
• Issue:
  1
• NIOSHTIC Number:
  nn:20067078
• Citation:
  J Immunotoxicol 2023 Dec; 20(1):2148782
• Contact Point Address:
  Jill A. Poole, Department of Allergy and Immunology, University of Nebraska Medical Center, 985910 Nebraska Medical Center,Omaha NE 68198-7400, USA
• Email:
  japoole@unmc.edu
• Federal Fiscal Year:
  2024
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center - Omaha
• Peer Reviewed:
  True
• Start Date:
  20110901
• Source Full Name:
  Journal of Immunotoxicology
• End Date:
  20270831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e02fc46c7542c7b0b286790d55d49d8373b7b25f97a1bcefa16069f5cb8afbebb1a988804056ca7bca2238046717db07c332964c858034cdc1bec87dd0da799f
• Download URL:
  https://stacks.cdc.gov/view/cdc/231277/cdc_231277_DS1.pdf
• File Type:
  [PDF - 1.98 MB ]