Differential responses of COPD macrophages to respiratory bacterial pathogens

COPD patients have increased susceptibility to airway bacterial colonisation. Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae are three of the most common respiratory bacterial species in COPD. H. influenzae colonisation, but not other bacteria, in COPD patients is associated with higher sputum neutrophil counts. Alveolar macrophages are key in clearance of bacteria as well as releasing mediators to recruit and activate other immune cells in response to infection. The aim was to characterise differences in COPD macrophage responses to H. influenzae, M. catarrhalis and S. pneumoniae, focusing on release of inflammatory and chemotactic mediators, and apoptosis regulation. Lung macrophages and monocyte-derived macrophages from COPD patients and control subjects were exposed to H. influenzae, M. catarrhalis or S. pneumoniae. Cytokine secretion (tumour necrosis factor-alpha, interleukin (1L)-6, CXCL8, CCL5 and IL-1 beta) were measured by ELISA and quantitative reverse transcriptase PCR (RT-qPCR), and apoptosis genes MCL-1, BCL-2, BAX and BAK1 by RT-qPCR. Apoptosis and reactive oxygen species (ROS) release were also measured. Macrophages responded differentially to the bacterial species, with increased, prolonged production of the neutrophil chemoattractant CXCL8 in response to H. influenzae and M. catarrhalis but not S. pneumoniae. S. pneumoniae initiated macrophage apoptosis and ROS release, H. influenzae and M. catarrhalis did not and increased anti-apoptosis gene expression (BCL-2 5.5-fold and MCL-1 2.4-fold, respectively). Differential cytokine responses of macrophages to these bacterial species can explain neutrophilic airway inflammation associated with H. influenzae, but not S. pneumoniae in COPD. Furthermore, delayed macrophage apoptosis is a potential mechanism contributing to inability to clear H. influenzae.

Automated summary

COPD patients have increased susceptibility to bacterial colonisation in the airways, with Haemophilus influenzae being associated with higher neutrophil counts. This study found that lung macrophages responded differently to different bacterial species, with increased production of the neutrophil chemoattractant CXCL8 in response to Haemophilus influenzae and Moraxella catarrhalis but not Streptococcus pneumoniae. Streptococcus pneumoniae induced macrophage apoptosis and ROS release, while Haemophilus influenzae and Moraxella catarrhalis increased anti-apoptosis gene expression. These differential responses of macrophages to different bacterial species can explain the airway inflammation associated with Haemophilus influenzae in COPD patients.