{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T19:27:40Z","timestamp":1789414060493,"version":"build-2803163510"},"reference-count":61,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002081","name":"Irish Research Council","doi-asserted-by":"publisher","award":["GOIPD\/2020\/16"],"award-info":[{"award-number":["GOIPD\/2020\/16"]}],"id":[{"id":"10.13039\/501100002081","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002081","name":"Irish Research Council","doi-asserted-by":"publisher","award":["EIA-2019-010"],"award-info":[{"award-number":["EIA-2019-010"]}],"id":[{"id":"10.13039\/501100002081","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Health Research Board","award":["GOIPD\/2020\/16"],"award-info":[{"award-number":["GOIPD\/2020\/16"]}]},{"name":"Health Research Board","award":["EIA-2019-010"],"award-info":[{"award-number":["EIA-2019-010"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neutrophils are dynamic cells, playing a critical role in pathogen clearance; however, neutrophil infiltration into the tissue can act as a double-edged sword. They are one of the primary sources of excessive inflammation during infection, which has been observed in many infectious diseases including pneumonia and active tuberculosis (TB). Neutrophil function is influenced by interactions with other immune cells within the inflammatory lung milieu; however, how these interactions affect neutrophil function is unclear. Our study examined the macrophage\u2013neutrophil axis by assessing the effects of conditioned medium (M\u03a6-CM) from primary human monocyte-derived macrophages (hMDMs) stimulated with LPS or a whole bacterium (Mycobacterium tuberculosis) on neutrophil function. Stimulated hMDM-derived M\u03a6-CM boosts neutrophil activation, heightening oxidative and glycolytic metabolism, but diminishes migratory potential. These neutrophils exhibit increased ROS production, elevated NET formation, and heightened CXCL8, IL-13, and IL-6 compared to untreated or unstimulated hMDM-treated neutrophils. Collectively, these data show that M\u03a6-CM from stimulated hMDMs activates neutrophils, bolsters their energetic profile, increase effector and inflammatory functions, and sequester them at sites of infection by decreasing their migratory capacity. These data may aid in the design of novel immunotherapies for severe pneumonia, active tuberculosis and other diseases driven by pathological inflammation mediated by the macrophage\u2013neutrophil axis.<\/jats:p>","DOI":"10.3390\/ijms25052898","type":"journal-article","created":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T11:19:24Z","timestamp":1709291964000},"page":"2898","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Human Macrophages Activate Bystander Neutrophils\u2019 Metabolism and Effector Functions When Challenged with Mycobacterium tuberculosis"],"prefix":"10.3390","volume":"25","author":[{"given":"Dearbhla M.","family":"Murphy","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine, School of Medicine, Trinity Translational Medicine Institute (TTMI), Trinity Centre for Health Sciences, St. James\u2019s Hospital, Trinity College Dublin, The University of Dublin, Dublin 8, D08 W9RT Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasija","family":"Walsh","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, School of Medicine, Trinity Translational Medicine Institute (TTMI), Trinity Centre for Health Sciences, St. James\u2019s Hospital, Trinity College Dublin, The University of Dublin, Dublin 8, D08 W9RT Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Stein","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, School of Medicine, Trinity Translational Medicine Institute (TTMI), Trinity Centre for Health Sciences, St. James\u2019s Hospital, Trinity College Dublin, The University of Dublin, Dublin 8, D08 W9RT Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea","family":"Petrasca","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute (TBSI), Trinity College Dublin, The University of Dublin, D02 R590 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donal J.","family":"Cox","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, School of Medicine, Trinity Translational Medicine Institute (TTMI), Trinity Centre for Health Sciences, St. James\u2019s Hospital, Trinity College Dublin, The University of Dublin, Dublin 8, D08 W9RT Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, School of Medicine, Trinity Translational Medicine Institute (TTMI), Trinity Centre for Health Sciences, St. James\u2019s Hospital, Trinity College Dublin, The University of Dublin, Dublin 8, D08 W9RT Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Duffin","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, School of Medicine, Trinity Translational Medicine Institute (TTMI), Trinity Centre for Health Sciences, St. James\u2019s Hospital, Trinity College Dublin, The University of Dublin, Dublin 8, D08 W9RT Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gr\u00e1inne","family":"Jameson","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, School of Medicine, Trinity Translational Medicine Institute (TTMI), Trinity Centre for Health Sciences, St. James\u2019s Hospital, Trinity College Dublin, The University of Dublin, Dublin 8, D08 W9RT Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah A.","family":"Connolly","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, School of Medicine, Trinity Translational Medicine Institute (TTMI), Trinity Centre for Health Sciences, St. James\u2019s Hospital, Trinity College Dublin, The University of Dublin, Dublin 8, D08 W9RT Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3641-4374","authenticated-orcid":false,"given":"Fiona","family":"O\u2019Connell","sequence":"additional","affiliation":[{"name":"Department of Surgery, Trinity St. James\u2019s Cancer Institute, Trinity Translational Medicine Institute (TTMI), St. James\u2019s Hospital, Dublin 8, D08 W9RT Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacintha","family":"O\u2019Sullivan","sequence":"additional","affiliation":[{"name":"Department of Surgery, Trinity St. James\u2019s Cancer Institute, Trinity Translational Medicine Institute (TTMI), St. James\u2019s Hospital, Dublin 8, D08 W9RT Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharee A.","family":"Basdeo","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, School of Medicine, Trinity Translational Medicine Institute (TTMI), Trinity Centre for Health Sciences, St. James\u2019s Hospital, Trinity College Dublin, The University of Dublin, Dublin 8, D08 W9RT Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5313-385X","authenticated-orcid":false,"given":"Joseph","family":"Keane","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, School of Medicine, Trinity Translational Medicine Institute (TTMI), Trinity Centre for Health Sciences, St. James\u2019s Hospital, Trinity College Dublin, The University of Dublin, Dublin 8, D08 W9RT Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9431-2002","authenticated-orcid":false,"given":"James 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