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(CM-COVID)","award":["01ZX1906A"],"award-info":[{"award-number":["01ZX1906A"]}]},{"name":"BIH (CM-COVID)","award":["01ZX1906B"],"award-info":[{"award-number":["01ZX1906B"]}]},{"name":"BIH (CM-COVID)","award":["01KX2021"],"award-info":[{"award-number":["01KX2021"]}]},{"name":"BIH (CM-COVID)","award":["01KX2121"],"award-info":[{"award-number":["01KX2121"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Community-acquired pneumonia remains a major contributor to global communicable disease-mediated mortality. Neutrophils play a leading role in trying to contain bacterial lung infection, but they also drive detrimental pulmonary inflammation, when dysregulated. Here we aimed at understanding the role of microRNA-223 in orchestrating pulmonary inflammation during pneumococcal pneumonia. Serum microRNA-223 was measured in patients with pneumococcal pneumonia and in healthy subjects. Pulmonary inflammation in wild-type and microRNA-223-knockout mice was assessed in terms of disease course, histopathology, cellular recruitment and evaluation of inflammatory protein and gene signatures following pneumococcal infection. Low levels of serum microRNA-223 correlated with increased disease severity in pneumococcal pneumonia patients. Prolonged neutrophilic influx into the lungs and alveolar spaces was detected in pneumococci-infected microRNA-223-knockout mice, possibly accounting for aggravated histopathology and acute lung injury. Expression of microRNA-223 in wild-type mice was induced by pneumococcal infection in a time-dependent manner in whole lungs and lung neutrophils. Single-cell transcriptome analyses of murine lungs revealed a unique profile of antimicrobial and cellular maturation genes that are dysregulated in neutrophils lacking microRNA-223. Taken together, low levels of microRNA-223 in human pneumonia patient serum were associated with increased disease severity, whilst its absence provoked dysregulation of the neutrophil transcriptome in murine pneumococcal pneumonia.<\/jats:p>","DOI":"10.3390\/cells12060959","type":"journal-article","created":{"date-parts":[[2023,3,22]],"date-time":"2023-03-22T07:46:43Z","timestamp":1679471203000},"page":"959","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["MicroRNA-223 Dampens Pulmonary Inflammation during Pneumococcal Pneumonia"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1616-4005","authenticated-orcid":false,"given":"Cengiz","family":"Goekeri","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"},{"name":"Faculty of Medicine, Cyprus International University, 99040 Nicosia, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8132-7237","authenticated-orcid":false,"given":"Peter","family":"Pennitz","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0646-3212","authenticated-orcid":false,"given":"Wibke","family":"Groenewald","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Behrendt","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3126-7950","authenticated-orcid":false,"given":"Holger","family":"Kirsten","sequence":"additional","affiliation":[{"name":"Institute for Medical Informatics, Statistics, and Epidemiology, Universit\u00e4t Leipzig, 04107 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6358-1215","authenticated-orcid":false,"given":"Christian M.","family":"Zobel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Bundeswehrkrankenhaus Berlin, 10115 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Berger","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gitta A.","family":"Heinz","sequence":"additional","affiliation":[{"name":"Therapeutic Gene Regulation, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), ein Institut der Leibniz-Gemeinschaft, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mir-Farzin","family":"Mashreghi","sequence":"additional","affiliation":[{"name":"Therapeutic Gene Regulation, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), ein Institut der Leibniz-Gemeinschaft, 10117 Berlin, Germany"},{"name":"Berlin Institute of Health at Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5655-4350","authenticated-orcid":false,"given":"Sandra-Maria","family":"Wienhold","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5667-6750","authenticated-orcid":false,"given":"Kristina","family":"Dietert","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Pathology, Freie Universit\u00e4t Berlin, 14163 Berlin, Germany"},{"name":"Veterinary Centre for Resistance Research (TZR), Freie Universit\u00e4t Berlin, 14163 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1739-749X","authenticated-orcid":false,"given":"Anca","family":"Dorhoi","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Friedrich-Loeffler-Institut, 17493 Greifswald-Insel Riems, Germany"},{"name":"Faculty of Mathematics and Natural Sciences, University of Greifswald, 17489 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4502-0393","authenticated-orcid":false,"given":"Achim D.","family":"Gruber","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Pathology, Freie Universit\u00e4t Berlin, 14163 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4059-1779","authenticated-orcid":false,"given":"Markus","family":"Scholz","sequence":"additional","affiliation":[{"name":"Institute for Medical Informatics, Statistics, and Epidemiology, Universit\u00e4t Leipzig, 04107 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5193-7755","authenticated-orcid":false,"given":"Gernot","family":"Rohde","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Medical Clinic I, Goethe-Universit\u00e4t Frankfurt am Main, 60596 Frankfurt am Main, Germany"},{"name":"CAPNETZ STIFTUNG, 30625 Hannover, Germany"},{"name":"Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), 30625 Hannover, 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of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"},{"name":"CAPNETZ STIFTUNG, 30625 Hannover, Germany"},{"name":"German Center for Lung Research (DZL), 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1973-3119","authenticated-orcid":false,"given":"Geraldine","family":"Nouailles","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Schirm, S., Ahnert, P., Wienhold, S., Mueller-Redetzky, H., Nouailles-Kursar, G., Loeffler, M., Witzenrath, M., and Scholz, 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