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

Details

• Alternative Title:
  J Immunotoxicol
• Personal Author:
  Johnson, Amber N. ; Dickinson, John ; Nelson, Amy ; Gaurav, Rohit ; Kudrna, Katrina ; Evans, Scott E. ; Janike, Katherine ; Wyatt, Todd A. ; Poole, Jill A.
• 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 |, 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)-α, 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.
• Subjects:
  Animals Dust Inhalation Exposure Interleukin-6 Mice Mice, Inbred C57BL Mucins Myeloid Differentiation Factor 88 Signal Transduction Toll-Like Receptors Tumor Necrosis Factor-alpha

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• Keywords:
  Adaptation Agriculture Airway Inflammation Environmental Respiratory Disease MyD88 Occupational Organic Dust
• Source:
  J Immunotoxicol. 20(1):2148782
• Pubmed ID:
  36538286
• Pubmed Central ID:
  PMC9912912
• Document Type:
  Journal Article
• Funding:
  R01 OH012045/OH/NIOSH CDC HHSUnited States/ ; IK6 BX005962/BX/BLRD VAUnited States/ ; P30 CA036727/CA/NCI NIH HHSUnited States/ ; R35 HL144805/HL/NHLBI NIH HHSUnited States/ ; R01 HL157269/HL/NHLBI NIH HHSUnited States/ ; R01 ES019325/ES/NIEHS NIH HHSUnited States/ ; U54 OH010162/OH/NIOSH CDC HHSUnited States/
• Volume:
  20
• Issue:
  1
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:e6329ad11278331bebd97f255dd53ef7c53d061c03724969344e2e66d49f77f751ea19866bc31bd29cce790d6ca526d1d515659128e5114dde64c0173f63a46d
• Download URL:
  https://stacks.cdc.gov/view/cdc/124597/cdc_124597_DS1.pdf
• File Type:
  [PDF - 1.24 MB ]