{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:52:07Z","timestamp":1791298327472,"version":"4.1.0"},"reference-count":70,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2011,11,1]],"date-time":"2011-11-01T00:00:00Z","timestamp":1320105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Streptococcus pneumoniae meningitis causes brain damage through inflammation-related pathways whose identity and mechanisms of action are yet unclear. We previously identified caspase-1, which activates precursor IL-1 type cytokines, as a central mediator of inflammation in pneumococcal meningitis. In this study, we demonstrate that lack of the inflammasome components ASC or NLRP3 that are centrally involved in caspase-1 activation decreases scores of clinical and histological disease severity as well as brain inflammation in murine pneumococcal meningitis. Using specific inhibitors (anakinra and rIL-18\u2013binding protein), we further show that ASC- and NLRP3-dependent pathologic alterations are solely related to secretion of both IL-1\u03b2 and IL-18. Moreover, using differentiated human THP-1 cells, we demonstrate that the pneumococcal pore-forming toxin pneumolysin is a key inducer of IL-1\u03b2 expression and inflammasome activation upon pneumococcal challenge. The latter depends on the release of ATP, lysosomal destabilization (but not disruption), and cathepsin B activation. The in vivo importance of this pathway is supported by our observation that the lack of pneumolysin and cathepsin B inhibition is associated with a better clinical course and less brain inflammation in murine pneumococcal meningitis. Collectively, our study indicates a central role of the NLRP3 inflammasome in the pathology of pneumococcal meningitis. Thus, interference with inflammasome activation might be a promising target for adjunctive therapy of this disease.<\/jats:p>","DOI":"10.4049\/jimmunol.1100790","type":"journal-article","created":{"date-parts":[[2011,10,14]],"date-time":"2011-10-14T23:49:51Z","timestamp":1318636191000},"page":"5440-5451","source":"Crossref","is-referenced-by-count":194,"title":["The NLRP3 Inflammasome Contributes to Brain Injury in Pneumococcal Meningitis and Is Activated through ATP-Dependent Lysosomal Cathepsin B Release"],"prefix":"10.1093","volume":"187","author":[{"given":"Tobias","family":"Hoegen","sequence":"first","affiliation":[{"name":"Department of Neurology, Clinic of the University of Munich , D-81377 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadin","family":"Tremel","sequence":"additional","affiliation":[{"name":"Department of Neurology, Clinic of the University of Munich , D-81377 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Neurology, Clinic of the University of Munich , D-81377 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Angele","sequence":"additional","affiliation":[{"name":"Department of Neurology, Clinic of the University of Munich , D-81377 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Wagner","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, Immunology, and Hygiene, Technical University of Munich , D-81675 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Kirschning","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology, University of Essen , D-45122 Essen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Walter","family":"Pfister","sequence":"additional","affiliation":[{"name":"Department of Neurology, Clinic of the University of Munich , D-81377 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano","family":"Fontana","sequence":"additional","affiliation":[{"name":"Institute for Experimental Immunology, University of Zurich , CH-8044 Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Hammerschmidt","sequence":"additional","affiliation":[{"name":"Department Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, Ernst Moritz Arndt University , D-17487 Greifswald ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Koedel","sequence":"additional","affiliation":[{"name":"Department of Neurology, Clinic of the University of Munich , D-81377 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,11,15]]},"reference":[{"key":"2025032410464477300_r1","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1056\/NEJMra052116","article-title":"Community-acquired bacterial meningitis in adults","volume":"354","author":"van de Beek","year":"2006","journal-title":"N. 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