{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T14:51:11Z","timestamp":1773499871056,"version":"3.50.1"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The pathomechanisms underlying the frequently observed fatal outcome of Klebsiella pneumoniae pneumonia in elderly patients are understudied. In this study, we examined the early antibacterial immune response in young mice (age 2\u20133 mo) as compared with old mice (age 18\u201319 mo) postinfection with K. pneumoniae. Old mice exhibited significantly higher bacterial loads in lungs and bacteremia as early as 24 h postinfection compared with young mice, with neutrophilic pleuritis nearly exclusively developing in old but not young mice. Moreover, we observed heavily increased cytokine responses in lungs and pleural spaces along with increased mortality in old mice. Mechanistically, Nlrp3 inflammasome activation and caspase-1\u2013dependent IL-1\u03b2 secretion contributed to the observed hyperinflammation, which decreased upon caspase-1 inhibitor treatment of K. pneumoniae\u2013infected old mice. Irradiated old mice transplanted with the bone marrow of young mice did not show hyperinflammation or early bacteremia in response to K. pneumoniae. Collectively, the accentuated lung pathology observed in K. pneumoniae\u2013infected old mice appears to be due to regulatory defects of the bone marrow but not the lung, while involving dysregulated activation of the Nlrp3\/caspase-1\/IL-1\u03b2 axis.<\/jats:p>","DOI":"10.4049\/jimmunol.2200413","type":"journal-article","created":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T17:49:45Z","timestamp":1666288185000},"page":"2172-2180","source":"Crossref","is-referenced-by-count":3,"title":["Neutrophilic Pleuritis Is a Severe Complication of <i>Klebsiella pneumoniae<\/i> Pneumonia in Old Mice"],"prefix":"10.1093","volume":"209","author":[{"given":"Femke D","family":"Hollwedel","sequence":"first","affiliation":[{"name":"Division of Experimental Pneumology, Hannover Medical School , Hannover,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regina","family":"Maus","sequence":"additional","affiliation":[{"name":"Division of Experimental Pneumology, Hannover Medical School , Hannover,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Stolper","sequence":"additional","affiliation":[{"name":"Division of Experimental Pneumology, Hannover Medical School , Hannover,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5251-2281","authenticated-orcid":false,"given":"Danny","family":"Jonigk","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Hannover Medical School , Hannover,","place":["Germany"]},{"name":"German Center for Lung Research, Partner Site Biomedical Research in Endstage and Obstructive Lung Disease Hannover , Hannover,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6139-8399","authenticated-orcid":false,"given":"Christina B","family":"Hildebrand","sequence":"additional","affiliation":[{"name":"Institute of Functional and Applied Anatomy, Hannover Medical School , Hannover,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9947-7356","authenticated-orcid":false,"given":"Tobias","family":"Welte","sequence":"additional","affiliation":[{"name":"German Center for Lung Research, Partner Site Biomedical Research in Endstage and Obstructive Lung Disease Hannover , Hannover,","place":["Germany"]},{"name":"Clinic for Pneumology, Hannover Medical School , Hannover,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Brandenberger","sequence":"additional","affiliation":[{"name":"German Center for Lung Research, Partner Site Biomedical Research in Endstage and Obstructive Lung Disease Hannover , Hannover,","place":["Germany"]},{"name":"Institute of Functional Anatomy, Charit\u00e9 University Medicine , Berlin,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich A","family":"Maus","sequence":"additional","affiliation":[{"name":"Division of Experimental Pneumology, Hannover Medical School , Hannover,","place":["Germany"]},{"name":"German Center for Lung Research, Partner Site Biomedical Research in Endstage and Obstructive Lung Disease Hannover , Hannover,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,12,1]]},"reference":[{"key":"2025021008440917100_r1","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1055\/s-0030-1265897","article-title":"The role of immunity and inflammation in lung senescence and susceptibility to infection in the elderly","volume":"31","author":"Meyer","year":"2010","journal-title":"Semin. 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