Abstract
Toll-like receptors (TLRs) and nucleotide-binding oligomerisation domain (NOD)-like receptors (NLRs) are two major forms of innate immune sensors but their role in the immunopathology of stable chronic obstructive pulmonary disease (COPD) is incompletely studied. Our objective here was to investigate TLR and NLR signalling pathways in the bronchial mucosa in stable COPD.
Using immunohistochemistry, the expression levels of TLR2, TLR4, TLR9, NOD1, NOD2, CD14, myeloid differentiation primary response gene 88 (MyD88), Toll-interleukin-1 receptor domain-containing adaptor protein (TIRAP), and the interleukin-1 receptor-associated kinases phospho-IRAK1 and IRAK4 were measured in the bronchial mucosa of subjects with stable COPD of different severity (n=34), control smokers (n=12) and nonsmokers (n=12). The bronchial bacterial load of Pseudomonas aeruginosa, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae was measured by quantitative real-time PCR.
TLR4 and NOD1 expression was increased in the bronchial mucosa of patients with severe/very severe stable COPD compared with control subjects. TLR4 bronchial epithelial expression correlated positively with CD4+ and CD8+ cells and airflow obstruction. NOD1 expression correlated with CD8+ cells. The bronchial load of P. aeruginosa was directly correlated, but H. influenzae inversely correlated, with the degree of airflow obstruction. Bacterial load did not correlate with inflammatory cells.
Bronchial epithelial overexpression of TLR4 and NOD1 in severe/very severe stable COPD, associated with increased bronchial inflammation and P. aeruginosa bacterial load, may play a role in the pathogenesis of COPD.
Abstract
Inflammation, bacterial load and active antibacterial immune response involving TLR4 and NOD1 in stable COPD http://ow.ly/S1fp308qcwp
Footnotes
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Support statement: This work was supported by Istituti Clinici Scientifici Maugeri, SpA Società Benefit, Ricerca Corrente. I.M. Adcock and P.J. Barnes are supported by Wellcome Trust grant 093080/Z/10/Z. I.M. Adcock, K.F. Chung and P.J. Barnes are supported by the National Institute for Health Research (NIHR) Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London. Funding information for this article has been deposited with the Open Funder Registry. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR or the Dept of Health.
Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com
- Received October 12, 2016.
- Accepted January 20, 2017.
- Copyright ©ERS 2017