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

Poole JA; Wyatt TA; Kielian T; Oldenburg P; Gleason AM; Bauer A; Golden G; West WW; Sisson JH; Romberger DJ
Am J Respir Cell Mol Biol 2011 Oct; 45(4):711-719
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.
Agriculture; Agricultural-workers; Agricultural-industry; Organic-dusts; Work-environment; Farmers; Respiratory-system-disorders; Animal-husbandry; Animal-husbandry-workers; Animals; Immune-reaction; Airway-resistance; Airway-obstruction; Dust-exposure; Dusts; Cellular-reactions; Proteins; Lung-cells; Lung-irritants; Pulmonary-function; Laboratory-animals; Laboratory-testing; Exposure-assessment; Exposure-methods; Methacholines; Pathology; Cytotoxic-effects; Author Keywords: Toll-like receptor 2; swine/pig facility; peptidoglycan; organic dust; lung pathology
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
Publication Date
Document Type
Journal Article
Email Address
Funding Type
Fiscal Year
Identifying No.
Grant-Number-R01-OH-008539; B12072011
Issue of Publication
Priority Area
Agriculture, Forestry and Fishing
Source Name
American Journal of Respiratory Cell and Molecular Biology
Performing Organization
University of Nebraska Medical Center, Omaha, Nebraska
Page last reviewed: March 18, 2022
Content source: National Institute for Occupational Safety and Health Education and Information Division