Toll-like receptor 2 regulates organic dust-induced airway inflammation

Details

• Personal Author:
  Bauer A ; Gleason AM ; Golden G ; Kielian T ; Oldenburg P ; Poole JA ; Romberger DJ ; Sisson JH ; West WW ; Wyatt TA
• Description:
  Organic dust exposure in agricultural environments results in significant airway inflammatory diseases. Gram-positive cell wall components are present in high concentrations in animal farming dusts, but their role in mediating dust-induced airway inflammation is not clear. This study investigated the role of Toll-like receptor (TLR) 2, a pattern recognition receptor for gram-positive cell wall products, in regulating swine facility organic dust extract (DE)-induced airway inflammation in mice. Isolated lung macrophages from TLR2 knockout mice demonstrated reduced TNF-a, IL-6, keratinocyte chemoattractant/CXCL1, but not macrophage inflammatory protein-2/CXCL2 expression, after DE stimulation ex vivo. Next, using an established mouse model of intranasal inhalation challenge, we analyzed bronchoalveolar lavage fluid and lung tissue in TLR2-deficient and wild-type (WT) mice after single and repetitive DE challenge. Neutrophil influx and select cytokines/chemokines were significantly lower in TLR2-deficient mice at 5 and 24 hours after single DE challenge. After daily exposure to DE for 2 weeks, there were significant reductions in total cellularity, neutrophil influx, and TNF-a, IL-6, CXCL1, but not CXCL2 expression, in TLR2-deficient mice as compared with WT animals. Lung pathology revealed that bronchiolar inflammation, but not alveolar inflammation, was reduced in TLR2-deficient mice after repetitive exposure. Airway hyperresponsiveness to methacholine after dust exposure was similar in both groups. Finally, airway inflammatory responses in WT mice after challenge with a TLR2 agonist, peptidoglycan, resembled DE-induced responses. Collectively, these results demonstrate that the TLR2 pathway is important in regulating swine facility organic dust-induced airway inflammation, which suggests the importance of TLR2 agonists in mediating large animal farming-induced airway inflammatory responses. [Description provided by NIOSH]
• Subjects:
  Agriculture Animal Husbandry Animals Cytotoxins Dust Environmental Monitoring Farmers Immune System Laboratories Lung Methacholine Compounds Occupational Health Pathology Respiratory System Respiratory Tract Diseases Safety Workplace

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• Keywords:
  Agricultural-industry Agricultural-workers Airway-obstruction Airway-resistance Animal-husbandry Animal-husbandry-workers Author Keywords: Toll-like Receptor 2 Cellular-reactions Cytotoxic-effects Dust-exposure Dusts Exposure-assessment Exposure-methods Immune-reaction Laboratory-animals Laboratory-testing Lung-cells Lung-irritants Lung Pathology Methacholines Organic-dusts Organic Dust Peptidoglycan Proteins Pulmonary-function Respiratory-system-disorders Swine/Pig Facility Work-environment

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• ISSN:
  1044-1549
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Nebraska ; OSHA Region 7
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  45
• Issue:
  4
• NIOSHTIC Number:
  nn:20039963
• Citation:
  Am J Respir Cell Mol Biol 2011 Oct; 45(4):711-719
• Contact Point Address:
  Jill A. Poole, M.D., Pulmonary, Critical Care, Sleep & Allergy Division; Department of Internal Medicine; University of Nebraska Medical Center; 985300 The Nebraska Medical Center Omaha, NE 68198-5300
• Email:
  japoole@unmc.edu
• Federal Fiscal Year:
  2012
• 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:
  American Journal of Respiratory Cell and Molecular Biology
• End Date:
  20160731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:8e987392d37601c1836d6d427ed0969830197fa2c9553e8a012e7bb3befaf491af797ffff6b36f55bd3e4238e4c3628a107a88f5a843220e0c67a7a6845729f5
• Download URL:
  https://stacks.cdc.gov/view/cdc/192990/cdc_192990_DS1.pdf
• File Type:
  [PDF - 1.40 MB ]