TLR4 and NOD1 increase in stable COPD of increasing severity. Relationship with tissutal bacterial load

Abstract

Background: The immune host response related to bacterial and viral infections in the airways and lung of COPD patients is unclear. Objectives: To investigate the expression of anti-bacterial and anti-viral antigens in bronchial biopsies and lung parenchyma of stable COPD patients in relation to bacterial load. Methods: Immunohistochemical (IHC) and qRT-PCR-expression of TLR2-3-4-7-8-9, NOD1, NOD2, MYD88, TRIF, TIRAP, pIRAK1, IRAK4, IRF3, pIRF3, IRF7, pIRF7, RIG1, MDA5, LGP2, MAVS, STING, DAI, IFNα and IFNβ was measured in bronchial mucosa in patients with mild/moderate (n=16), severe/very severe (n=18) stable COPD, control smokers (n=12) and control non-smokers (n=12). Selected relevant antigens were measured by IHC in peripheral lung from COPD (n=12) and control smokers (n=12) and in the bronchoalveolar lavage (BAL) supernatant. Total bacterial load (16S), P. aeruginosa , H. influenzae , M. catarralis , S. pneumonie were measured by qRT-PCR in bronchial biopsies of COPD and control subjects. Results: In bronchial biopsies TLR4+ and NOD1+ epithelial cells were increased in severe/very severe COPD patients compared to both control groups as did NOD1+ cells in lamina propria. qRT-PCR showed increased MDA5 and STING mRNA levels in severe/very severe COPD compared to control smokers. Total bacterial load (16S/mm 3 ) and P. aeruginosa /mm 3 were reduced in severe/very severe COPD compared to both control groups. In peripheral lung tissue and in the BAL supernatant TLR4, NOD1, IFNα and IFNβ were similarly expressed in COPD patients and control subjects. Conclusions: Increased expression of TLR4 and NOD1 in the bronchial mucosa may be relevant in the progression of COPD.