Bronchial inflammation and bacterial load in stable COPD is associated with TLR4 overexpression

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 ,, and 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 was directly correlated, but 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 bacterial load, may play a role in the pathogenesis of COPD.

Inflammatory endotypes in COPD

“…The chemokines CXCL9 (Mig), CXCL10 (IP‐10) and CXCL11 (I‐TAC), which all bind to CXCR3 expressed on CD4 + and CD8 + T cells are increased in sputum of patients with COPD and T cells and monocytes show enhanced migration to these chemokines . CD8 + cells in lung express increased bacterial Toll‐like receptors (TLR), indicating that they may be regulated by colonizing bacteria . There is also an increase in innate lymphoid cells, particularly ILC1 and ILC3 cells .…”

The lung microbiome: clinical and therapeutic implications

“…In COPD, a multitude of bacteria, including potential respiratory pathogens, is often present. In addition, with increasing degrees of airflow limitation, there is also an increased recovery of opportunistic pathogens such as Pseudomonas aeruginosa [46]. This bacterial colonization correlates with the severity of inflammatory response, radiological changes, pathological variations of a local immune response, and increased daily symptoms [47].…”

miRNA-486-5p Promotes COPD Progression by Targeting HAT1 to Regulate the TLR4-Triggered Inflammatory Response of Alveolar Macrophages

“…Reportedly, TLR4 could promote airway neutrophilia in COPD [10], and tagging single nucleotide polymorphisms in TLR4 was related to sputum in ammatory cell induction and lung function decline [11]. A previous study revealed that TLR4 was highly expressed in bronchial mucosa of severe COPD patients compared to health individuals, and its overexpression was positively correlated with CD4+/CD8+ cell in ltration and air ow obstruction [12]. These results suggested TLR4's important role in COPD pathogenesis and progression.…”