{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:02:32Z","timestamp":1791442952390,"version":"4.3.3"},"reference-count":86,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T00:00:00Z","timestamp":1689724800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["German Center for Lung Research"],"award-info":[{"award-number":["German Center for Lung Research"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["PRACTIS Clinician Scientist Programme of Hannover Medical School (ME 3696\/3-1)"],"award-info":[{"award-number":["PRACTIS Clinician Scientist Programme of Hannover Medical School (ME 3696\/3-1)"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["Germany\u2019s Excellence Strategy \u2013 EXC 2155 \u2018RESIST\u2019 \u2013 Project ID 390874280"],"award-info":[{"award-number":["Germany\u2019s Excellence Strategy \u2013 EXC 2155 \u2018RESIST\u2019 \u2013 Project ID 390874280"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>S100A8\/A9 has important immunomodulatory roles in antibacterial defense, but its relevance in focal pneumonia caused by <jats:italic>Streptococcus pneumoniae<\/jats:italic> (<jats:italic>S<\/jats:italic>. <jats:italic>pneumoniae<\/jats:italic>) is understudied. We show that S100A9 was significantly increased in BAL fluids of patients with bacterial but not viral pneumonia and correlated with procalcitonin and sequential organ failure assessment scores. Mice deficient in S100A9 exhibited drastically elevated Zn<jats:sup>2+<\/jats:sup> levels in lungs, which led to bacterial outgrowth and significantly reduced survival. In addition, reduced survival of S100A9 KO mice was characterized by excessive release of neutrophil elastase, which resulted in degradation of opsonophagocytically important collectins surfactant proteins A and D. All of these features were attenuated in <jats:italic>S<\/jats:italic>. <jats:italic>pneumoniae<\/jats:italic>-challenged chimeric WT\u2192S100A9 KO mice. Similarly, therapy of <jats:italic>S<\/jats:italic>. <jats:italic>pneumoniae<\/jats:italic>-infected S100A9 KO mice with a mutant S100A8\/A9 protein showing increased half-life significantly decreased lung bacterial loads and lung injury. Collectively, S100A9 controls central antibacterial immune mechanisms of the lung with essential relevance to survival of pneumococcal pneumonia. Moreover, S100A9 appears to be a promising biomarker to distinguish patients with bacterial from those with viral pneumonia.<\/jats:p>\n<jats:p><jats:bold>Trial registration<\/jats:bold>: Clinical Trials register (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/drks.de\/search\/en\/trial\/DRKS00000620\" xlink:type=\"simple\">DRKS00000620<\/jats:ext-link>).<\/jats:p>","DOI":"10.1371\/journal.ppat.1011493","type":"journal-article","created":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T17:35:39Z","timestamp":1689788139000},"page":"e1011493","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["S100A9 is indispensable for survival of pneumococcal pneumonia in mice"],"prefix":"10.1371","volume":"19","author":[{"given":"Lena","family":"Ostermann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Seeliger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha","family":"David","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolin","family":"Flasche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina","family":"Maus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieke S.","family":"Reinboth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Christmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin","family":"Neumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Korbinian","family":"Brand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Seltmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"B\u00fchling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Paton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Roth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Vogl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothee","family":"Viemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Welte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6172-8746","authenticated-orcid":true,"given":"Ulrich A.","family":"Maus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,7,19]]},"reference":[{"issue":"1","key":"ppat.1011493.ref001","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1136\/thx.2009.129502","article-title":"Clinical and economic burden of community-acquired pneumonia among adults in Europe","volume":"67","author":"T Welte","year":"2012","journal-title":"Thorax"},{"issue":"2","key":"ppat.1011493.ref002","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1086\/648678","article-title":"Etiology of community-acquired pneumonia: increased microbiological yield with new diagnostic methods. 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