TY - JOUR
T1 - Toll-like receptor 2 regulates organic dust-induced airway inflammation
AU - Poole, Jill A.
AU - Wyatt, Todd A.
AU - Kielian, Tammy
AU - Oldenburg, Peter
AU - Gleason, Angela M.
AU - Bauer, Ashley
AU - Golden, Gregory
AU - West, William W.
AU - Sisson, Joseph H.
AU - Romberger, Debra J.
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2011/10/1
Y1 - 2011/10/1
N2 - 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.
AB - 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.
KW - Lung pathology
KW - Organic dust
KW - Peptidoglycan
KW - Swine/pig facility
KW - Toll-like receptor 2
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U2 - 10.1165/rcmb.2010-0427OC
DO - 10.1165/rcmb.2010-0427OC
M3 - Article
C2 - 21278324
AN - SCOPUS:80053626935
SN - 1044-1549
VL - 45
SP - 711
EP - 719
JO - American journal of respiratory cell and molecular biology
JF - American journal of respiratory cell and molecular biology
IS - 4
ER -