@article {Lea00044-2022, author = {Simon Lea and Augusta Beech and James Baker and Rosemary Gaskell and Dharmendra Pindolia and Aisha Baba Dikwa and Rajesh Shah and Dave Singh}, title = {Differential responses of COPD macrophages to respiratory bacterial pathogens}, elocation-id = {00044-2022}, year = {2022}, doi = {10.1183/23120541.00044-2022}, publisher = {European Respiratory Society}, abstract = {COPD patients have increased susceptibility to airway bacterial colonisation. Haemophilus influenzae (H. influenzae), Moraxella catarrhalis (M. catarrhalis) and Streptococcus pneumoniae (S. 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 (TNF-α, IL-6, CXCL8, CCL5 and IL-1β) were measured by ELISA and RT-qPCR, and apoptosis genes MCL-1, BCL-2, BAX and BAK1 by RT-qPCR. Apoptosis and 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 (BCL-2 5.5 fold and MCL-1 2.4 fold respectively) expression.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.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: Simon Lea has nothing to disclose.Conflict of interest: Augusta Beech has nothing to disclose.Conflict of interest: James Baker has nothing to disclose.Conflict of interest: Rosemary Gaskell has nothing to disclose.Conflict of interest: Dharmendra Pindolia has nothing to disclose.Conflict of interest: Aisha Baba Dikwa has nothing to disclose.Conflict of interest: Rajesh Shah has nothing to disclose.Conflict of interest: Dave Singh has received sponsorship to attend and speak at international meetings, honoraria for lecturing or attending advisory boards from the following companies: Aerogen, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, CSL Behring, Epiendo, Genentech, GlaxoSmithKline, Glenmark, Gossamerbio, Kinaset, Menarini, Novartis, Pulmatrix, Sanofi, Teva, Theravance and Verona.}, URL = {https://openres.ersjournals.com/content/early/2022/05/05/23120541.00044-2022}, eprint = {https://openres.ersjournals.com/content/early/2022/05/05/23120541.00044-2022.full.pdf}, journal = {ERJ Open Research} }