{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T04:21:40Z","timestamp":1792383700552,"version":"4.4.0"},"reference-count":90,"publisher":"American Society for Clinical Investigation","issue":"6","license":[{"start":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T00:00:00Z","timestamp":1711065600000},"content-version":"vor","delay-in-days":36,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"crossref","award":["KO1974\/7-1,KI-596\/6-1"],"award-info":[{"award-number":["KO1974\/7-1,KI-596\/6-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,22]]},"abstract":"<jats:p>\n                    Despite effective antibiotic therapy, brain-destructive inflammation often cannot be avoided in pneumococcal meningitis. The causative signals are mediated predominantly through TLR-recruited myeloid differentiation primary response adaptor 88 (MyD88), as indicated by a dramatic pneumococcal meningitis phenotype of\n                    <jats:italic>\n                      Myd88\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice. Because lipoproteins and single-stranded RNA are crucial for recognition of Gram-positive bacteria such as\n                    <jats:italic>Streptococcus<\/jats:italic>\n                    <jats:italic>pneumoniae<\/jats:italic>\n                    by the host immune system, we comparatively analyzed the disease courses of\n                    <jats:italic>\n                      Myd88\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    and\n                    <jats:italic>\n                      Tlr2\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                      Tlr13\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice. Their phenotypic resemblance indicated TLR2 and -13 as master sensors of\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>pneumoniae<\/jats:italic>\n                    in the cerebrospinal fluid. A neutralizing anti-TLR2 antibody (T2.5) and chloroquine (CQ) \u2014 the latter applied here as an inhibitor of murine TLR13 and its human ortholog TLR8 \u2014 abrogated activation of murine and human primary immune cells exposed to antibiotic-treated\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>pneumoniae<\/jats:italic>\n                    . The inhibitory effect of the T2.5\/CQ cocktail was stronger than that of dexamethasone, the current standard adjunctive drug for pneumococcal meningitis. Accordingly, TLR2\/TLR13 blockade concomitant with ceftriaxone application significantly improved the clinical course of pneumococcal meningitis compared with treatment with ceftriaxone alone or in combination with dexamethasone. Our study indicates the importance of murine TLR13 and human TLR8, besides TLR2, in pneumococcal meningitis pathology, and suggests their blockade as a promising antibiotic therapy adjunct.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.165737","type":"journal-article","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T12:00:48Z","timestamp":1707998448000},"source":"Crossref","is-referenced-by-count":6,"title":["Combining antibiotic with anti-TLR2\/TLR13 therapy prevents brain pathology in pneumococcal meningitis"],"prefix":"10.1172","volume":"9","author":[{"given":"Susanne","family":"Dyckhoff-Shen","sequence":"first","affiliation":[{"name":"Department of Neurology, LMU University Hospital, LMU Munich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilias","family":"Masouris","sequence":"additional","affiliation":[{"name":"Department of Neurology, LMU University Hospital, LMU Munich, 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