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
Agriculture, Forestry and Fishing
American Journal of Respiratory Cell and Molecular Biology
University of Nebraska Medical Center, Omaha, Nebraska