{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T15:56:46Z","timestamp":1773763006977,"version":"3.50.1"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Research, Technology and Space","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010564","name":"German Center for Lung Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>We recently showed that S100A9 is indispensable for lung antibacterial immunity, making it crucial for the survival of pneumococcal pneumonia. However, the role of S100A8 in lung antibacterial immunity is ill-defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>S100A8 levels in the bronchoalveolar lavage fluid (BALF) of patients with pneumonia were quantified by enzyme-linked immunosorbent assay. Wild type and S100A8 knockout mice were orotracheally infected with Streptococcus pneumoniae, and bacterial clearance, disease progression, lung histopathology, and leukocyte recruitment were analyzed at defined time points.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>S100A8 protein levels were particularly increased in the BALF of patients with bacterial pneumonia as compared with viral pneumonia. Similarly, wild type mice responded with S100A8 and S100A9 protein release upon pneumococcal challenge. However, S100A8 deficiency led to decreased S100A9 levels and significantly increased bacterial loads in the lungs of S pneumoniae\u2013challenged mice. S pneumoniae\u2013infected S100A8 knockout mice developed a severe neutrophil-dominated purulent bronchopneumonia with interstitial and alveolar edema and intravascular coagulation, leading to early mortality. Mechanistically, S100A8 deficiency resulted in neutrophil elastase (NE)\u2013dependent degradation of surfactant proteins A and D in the lungs of mice. Incubation of wild type BALF with recombinant NE confirmed NE-dependent surfactant protein D degradation in vitro, which could be blocked by the NE-specific inhibitor sivelestat. Therapy with recombinant S100A8\/A9 protein rescued S100A8 knockout mice from fatal pneumococcal pneumonia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Deletion of S100A8 disturbs lung-protective immunity against S pneumoniae in mice. At the same time, analysis of the S100A8\/A9 protein complex in clinical samples may help to distinguish patients with bacterial vs viral pneumonia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiaf647","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T13:03:44Z","timestamp":1766581424000},"page":"445-457","source":"Crossref","is-referenced-by-count":0,"title":["Lack of S100A8 Impairs Lung-Protective Immunity Against\n                    <i>Streptococcus pneumoniae<\/i>"],"prefix":"10.1093","volume":"233","author":[{"given":"Lena","family":"Ostermann","sequence":"first","affiliation":[{"name":"Division of Experimental Pneumology, Hannover Medical School, Hannover ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Seeliger","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Hannover Medical School, Hannover 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Hospital Bonn, Bonn ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konstantin","family":"Neumann","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry, Hannover Medical School , Hannover ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Korbinian","family":"Brand","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry, Hannover Medical School , Hannover ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7177-7763","authenticated-orcid":false,"given":"Philippe A","family":"Tessier","sequence":"additional","affiliation":[{"name":"Infectious and Immune Diseases Division, CHU de Qu\u00e9bec\u2013Universit\u00e9 Laval Research Center, Laval University, Qu\u00e9bec City, Qu\u00e9bec ,","place":["Canada"]},{"name":"Department of Microbiology\u2013Infectious Diseases and Immunology, Faculty of 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