Abstract

Organic dust exposure in agricultural environments results in significant airway inflammatory diseases. Gram-positive cell wall components are present inhigh 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-α, IL-6, keratinocyte chemo-attractant/ 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-α, 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.

Original languageEnglish (US)
Pages (from-to)711-719
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Volume45
Issue number4
DOIs
StatePublished - Oct 1 2011

Fingerprint

Toll-Like Receptor 2
Dust
Inflammation
Animals
Agriculture
Lung
Cell Wall
Interleukin-6
Neutrophils
Swine
Cells
Chemokine CXCL2
Pattern Recognition Receptors
Wild Animals
Methacholine Chloride
Peptidoglycan
Macrophages
Bronchoalveolar Lavage Fluid
Pathology
Cellular Structures

Keywords

  • Lung pathology
  • Organic dust
  • Peptidoglycan
  • Swine/pig facility
  • Toll-like receptor 2

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Cite this

Toll-like receptor 2 regulates organic dust-induced airway inflammation. / Poole, Jill A; Wyatt, Todd A; Kielian, Tammy L; Oldenburg, Peter J; Gleason, Angela M.; Bauer, Ashley; Golden, Gregory; West, William W.; Sisson, Joseph Harold; Romberger, Debra.

In: American journal of respiratory cell and molecular biology, Vol. 45, No. 4, 01.10.2011, p. 711-719.

Research output: Contribution to journalArticle

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abstract = "Organic dust exposure in agricultural environments results in significant airway inflammatory diseases. Gram-positive cell wall components are present inhigh 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-α, IL-6, keratinocyte chemo-attractant/ 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-α, 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.",
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