MyD88 Regulates a Prolonged Adaptation Response to Environmental Dust Exposure-Induced Lung Disease

Details

• Personal Author:
  Dickinson JD ; Duryee MJ ; Gaurav R ; Glover SC ; Harkema JR ; Johnson AN ; Kalil J ; Kielian T ; Kumar B ; Nelson AJ ; Poole JA ; Romberger DJ ; Singh AB ; Tang Y ; Thiele GM
• Description:
  Background: Environmental organic dust exposures enriched in Toll-like receptor (TLR) agonists can reduce allergic asthma development but are associated with occupational asthma and chronic bronchitis. The TLR adaptor protein myeloid differentiation factor88 (MyD88) is fundamental in regulating acute inflammatory responses to organic dust extract (ODE), yet its role in repetitive exposures is unknown and could inform future strategies. Methods: Wild-type (WT) and MyD88 knockout (KO) mice were exposed intranasally to ODE or saline daily for 3 weeks (repetitive exposure). Repetitively exposed animals were also subsequently rested with no treatments for 4 weeks followed by single rechallenge with saline/ODE. Results: Repetitive ODE exposure induced neutrophil influx and release of pro-inflammatory cytokines and chemokines were profoundly reduced in MyD88 KO mice. In comparison, ODE-induced cellular aggregates, B cells, mast cell infiltrates and serum IgE levels remained elevated in KO mice and mucous cell metaplasia was increased. Expression of ODE-induced tight junction protein(s) was also MyD88-dependent. Following recovery and then rechallenge with ODE, inflammatory mediators, but not neutrophil influx, was reduced in WT mice pretreated with ODE coincident with increased expression of IL-33 and IL-10, suggesting an adaptation response. Repetitively exposed MyD88 KO mice lacked inflammatory responsiveness upon ODE rechallenge. Conclusions: MyD88 is essential in mediating the classic airway inflammatory response to repetitive ODE, but targeting MyD88 does not reduce mucous cell metaplasia, lymphocyte influx, or IgE responsiveness. TLR-enriched dust exposures induce a prolonged adaptation response that is largely MyD88-independent. These findings demonstrate the complex role of MyD88-dependent signaling during acute vs. chronic organic dust exposures. [Description provided by NIOSH]
• Subjects:
  Agriculture Antibodies Asthma, Occupational Dust Immune System Laboratories Lung Microbiology Occupational Exposure Occupational Health Respiratory System Safety

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• Keywords:
  Adaptation Airway Inflammation Author Keywords: Environmental Respiratory And Skin Disease Bronchitis Cell Signaling Chronic Exposure Cytokines Dust Exposure Dusts Exposure Assessment Immune Reaction Immunoglobulins Laboratory Animals Lung Cells Microorganisms MyD88 Occupational Occupational Asthma Organic Dust Organic Dusts Proteins

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• ISSN:
  1465-9921
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Florida ; Michigan ; Mississippi ; Nebraska ; OSHA Region 4 ; OSHA Region 5 ; OSHA Region 7
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  97
• Volume:
  21
• NIOSHTIC Number:
  nn:20059394
• Citation:
  Respir Res 2020 Apr; 21:97
• Contact Point Address:
  Jill A. Poole, Department of Internal Medicine, University of Nebraska Medical Center, 985990 Nebraska Medical Center, Omaha, NE 68198-5990, USA
• Email:
  japoole@unmc.edu
• Federal Fiscal Year:
  2020
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center - Omaha
• Peer Reviewed:
  True
• Start Date:
  20110901
• Source Full Name:
  Respiratory Research
• End Date:
  20270831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:a7fbf347d6b9e047ce930027d11396e671d9bdfeef97eaedae8e5e7c7ecbbc606be9b398f97c20beae510cfe432326f6149a90618bdecc995c22784f0164dca9
• Download URL:
  https://stacks.cdc.gov/view/cdc/223649/cdc_223649_DS1.pdf
• File Type:
  [PDF - 3.33 MB ]