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 associa...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
European Respiratory Society
2022-08-01
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| Series: | ERJ Open Research |
| Online Access: | http://openres.ersjournals.com/content/8/3/00044-2022.full |
| _version_ | 1827931478825107456 |
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| author | Simon Lea Augusta Beech James Baker Rosemary Gaskell Dharmendra Pindolia Aisha Baba Dikwa Rajesh Shah Dave Singh |
| author_facet | Simon Lea Augusta Beech James Baker Rosemary Gaskell Dharmendra Pindolia Aisha Baba Dikwa Rajesh Shah Dave Singh |
| author_sort | Simon Lea |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T06:53:17Z |
| format | Article |
| id | doaj.art-f11c0460d72d41dc85018fe6a9312c3f |
| institution | Directory Open Access Journal |
| issn | 2312-0541 |
| language | English |
| last_indexed | 2024-03-13T06:53:17Z |
| publishDate | 2022-08-01 |
| publisher | European Respiratory Society |
| record_format | Article |
| series | ERJ Open Research |
| spelling | doaj.art-f11c0460d72d41dc85018fe6a9312c3f2023-06-07T13:30:19ZengEuropean Respiratory SocietyERJ Open Research2312-05412022-08-018310.1183/23120541.00044-202200044-2022Differential responses of COPD macrophages to respiratory bacterial pathogensSimon Lea0Augusta Beech1James Baker2Rosemary Gaskell3Dharmendra Pindolia4Aisha Baba Dikwa5Rajesh Shah6Dave Singh7 Division 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 Division 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 Division 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 Division 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 Division 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 Division 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 Dept of Thoracic Surgery, Manchester University Hospital NHS Foundation Trust, Manchester, UK Division 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 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.http://openres.ersjournals.com/content/8/3/00044-2022.full |
| spellingShingle | Simon Lea Augusta Beech James Baker Rosemary Gaskell Dharmendra Pindolia Aisha Baba Dikwa Rajesh Shah Dave Singh Differential responses of COPD macrophages to respiratory bacterial pathogens ERJ Open Research |
| title | Differential responses of COPD macrophages to respiratory bacterial pathogens |
| title_full | Differential responses of COPD macrophages to respiratory bacterial pathogens |
| title_fullStr | Differential responses of COPD macrophages to respiratory bacterial pathogens |
| title_full_unstemmed | Differential responses of COPD macrophages to respiratory bacterial pathogens |
| title_short | Differential responses of COPD macrophages to respiratory bacterial pathogens |
| title_sort | differential responses of copd macrophages to respiratory bacterial pathogens |
| url | http://openres.ersjournals.com/content/8/3/00044-2022.full |
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