MyD88 in lung resident cells governs airway inflammatory and pulmonary function responses to organic dust treatment

Details

• Personal Author:
  Kielian T ; Poole JA ; Reynolds SJ ; Romberger DJ ; Simet S ; Sisson JH ; Staab E ; Wyatt TA
• Description:
  Inhalation of organic dusts within agriculture environments contributes to the development and/or severity of airway diseases, including asthma and chronic bronchitis. MyD88 KO (knockout) mice are nearly completely protected against the inflammatory and bronchoconstriction effects induced by acute organic dust extract (ODE) treatments. However, the contribution of MyD88 in lung epithelial cell responses remains unclear. In the present study, we first addressed whether ODE-induced changes in epithelial cell responses were MyD88-dependent by quantitating ciliary beat frequency and cell migration following wounding by electric cell-substrate impedance sensing. We demonstrate that the normative ciliary beat slowing response to ODE is delayed in MyD88 KO tracheal epithelial cells as compared to wild type (WT) control. Similarly, the normative ODE-induced slowing of cell migration in response to wound repair was aberrant in MyD88 KO cells. Next, we created MyD88 bone marrow chimera mice to investigate the relative contribution of MyD88-dependent signaling in lung resident (predominately epithelial cells) versus hematopoietic cells. Importantly, we demonstrate that ODE-induced airway hyperresponsiveness is MyD88-dependent in lung resident cells, whereas MyD88 action in hematopoietic cells is mainly responsible for ODE-induced TNF-alpha release. MyD88 signaling in lung resident and hematopoietic cells are necessary for ODE-induced IL-6 and neutrophil chemoattractant (CXCL1 and CXCL2) release and neutrophil influx. Collectively, these findings underscore an important role for MyD88 in lung resident cells for regulating ciliary motility, wound repair and inflammatory responses to ODE, and moreover, show that airway hyperresponsiveness appears uncoupled from airway inflammatory consequences to organic dust challenge in terms of MyD88 involvement. [Description provided by NIOSH]
• Subjects:
  Agriculture Chronic Disease Dust Immune System Laboratories Lung Lung Diseases Occupational Health Respiratory System Safety
• Keywords:
  Airway-obstruction Chronic-inflammation Dust-exposure Immune-reaction Inhalation Laboratory-animals Lung-cells Lung-disorders Lung-function Organic-dusts
• ISSN:
  1465-9921
• Document Type:
  Text
• Funding:
  Grant ; Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Colorado ; Nebraska ; OSHA Region 7 ; OSHA Region 8
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  16
• NIOSHTIC Number:
  nn:20047343
• Citation:
  Respir Res 2015 Sep; 16:111
• Contact Point Address:
  Jill A. Poole, M.D., Pulmonary, Critical Care, Sleep, and Allergy Division, Department of Medicine, University of Nebraska Medical Center, 985300 Nebraska Medical Center, Omaha, NE 68198-5990, USA
• Email:
  japoole@unmc.edu
• Federal Fiscal Year:
  2015
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center, Omaha, Nebraska
• Peer Reviewed:
  True
• Start Date:
  20060801
• Source Full Name:
  Respiratory Research
• End Date:
  20160731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:0cdcc5c8a66ca727255b6403128457354cc0d2f48613f3dbfcc9bec6fef9354677c40b35aa12b72d9bedc46bc140f66fe799c3dd1262ba4bfa6b0b7f3fc5b43d
• Download URL:
  https://stacks.cdc.gov/view/cdc/202448/cdc_202448_DS1.pdf
• File Type:
  [PDF - 795.01 KB ]