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Published on: February 22, 2017
Differential responses of COPD macrophages to respiratory bacterial pathogens
Simon Lea1, Augusta Beech1,2, James Baker1
1Division of Immunology, Immunity to Infection and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.
Abstract:
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-α, interleukin (IL)-6, CXCL8, CCL5 and IL-1β) 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.
Insights
In chronic obstructive pulmonary disease (COPD), macrophages respond differently to common bacteria. Haemophilus influenzae and Moraxella catarrhalis trigger inflammation, while Streptococcus pneumoniae induces cell death, impacting bacterial clearance.
Area of Science:
- Immunology
- Respiratory Medicine
- Microbiology
Background:
- Chronic obstructive pulmonary disease (COPD) patients are prone to airway bacterial colonization by common respiratory pathogens.
- Alveolar macrophages are crucial for bacterial clearance and orchestrating immune responses during respiratory infections.
- Previous studies suggest a link between Haemophilus influenzae colonization and increased sputum neutrophils in COPD.
Purpose of the Study:
- To investigate differential responses of COPD macrophages to Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae.
- To characterize the release of inflammatory and chemotactic mediators by macrophages upon bacterial exposure.
- To analyze the regulation of apoptosis and reactive oxygen species (ROS) in macrophages in response to these bacteria.
Main Methods:
- Lung and monocyte-derived macrophages from COPD patients and controls were exposed to H. influenzae, M. catarrhalis, or S. pneumoniae.
- Cytokine secretion (TNF-α, IL-6, CXCL8, CCL5, IL-1β) was measured using ELISA and RT-qPCR.
- Apoptosis-related gene expression (MCL-1, BCL-2, BAX, BAK1), apoptosis, and ROS release were quantified.
Main Results:
- Macrophages exhibited distinct cytokine profiles; prolonged CXCL8 production was observed in response to H. influenzae and M. catarrhalis, but not S. pneumoniae.
- S. pneumoniae induced macrophage apoptosis and ROS release, whereas H. influenzae and M. catarrhalis did not, instead upregulating anti-apoptotic genes (BCL-2, MCL-1).
- Differential macrophage responses correlate with observed neutrophilic inflammation in COPD.
Conclusions:
- Differential cytokine responses of macrophages to specific bacterial species explain the varying degrees of neutrophilic airway inflammation in COPD.
- The ability of H. influenzae and M. catarrhalis to delay macrophage apoptosis may contribute to impaired bacterial clearance in COPD patients.
- Understanding these macrophage-bacterial interactions is vital for developing targeted therapies for COPD exacerbations.
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