{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:12:17Z","timestamp":1792026737888,"version":"4.4.0"},"reference-count":129,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014717","name":"National Outstanding Youth Science Fund Project of National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014717","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Bacterial meningitis represents a devastating inflammatory disease of the central nervous system (CNS), characterized by the invasion of pathogens across the blood-brain barrier (BBB) and subsequent dysregulated immune responses. Key inflammatory mechanisms include pathogen recognition by microglial TLRs and NLRP3, neutrophil infiltration, and cytokine storms such as IL-1\u03b2 and TNF-\u03b1, leading to BBB disruption, cerebral edema, and neuronal injury. Despite antimicrobial therapy, excessive inflammation often results in neurological sequelae. Emerging strategies target immunomodulation through inflammasome inhibitors and BBB preservation using nanoparticle drug delivery to mitigate inflammation-driven CNS damage. This review focuses on the intricate interplay between bacterial virulence factors and neuroinflammatory cascades, with particular emphasis on\n                    <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n                    as a model pathogen. By integrating recent advances in molecular pathogenesis and translational immunology, this review provides a framework for developing precision therapies to mitigate inflammation-mediated CNS damage in bacterial meningitis.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2025.1628503","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T06:57:12Z","timestamp":1767769032000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Molecular mechanisms of streptococcal disruption of the blood-brain barrier and their pathogenic role in bacterial meningitis"],"prefix":"10.3389","volume":"16","author":[{"given":"Yumei","family":"Shi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benhai","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fmedt.2025.1497512","article-title":"Molecular diagnostic methods for rapid diagnosis of central nervous system infections","volume":"7","author":"Venkatareddy","year":"2025","journal-title":"Front Med Technol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.1106596","article-title":"Streptococcus pneumoniae meningitis and the CNS barriers","volume":"12","author":"Gil","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24032852","article-title":"Blood-brain barrier integrity damage in bacterial meningitis: the underlying link, mechanisms, and therapeutic targets","volume":"24","author":"Yang","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/jpids\/piae103","article-title":"Mechanisms and manifestations of group B streptococcus meningitis in newborns","volume":"14","author":"Alexander","year":"2025","journal-title":"J Pediatr Infect Dis Soc"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2024.07.004","article-title":"From cytokines to chemokines: Understanding inflammatory signaling in bacterial meningitis","volume":"173","author":"Ibrahim","year":"2024","journal-title":"Mol Immunol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"4946","DOI":"10.1016\/j.cell.2024.07.002","article-title":"The choroid plexus synergizes with immune cells during neuroinflammation","volume":"187","author":"Xu","year":"2024","journal-title":"Cell"},{"key":"B7","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1007\/s00701-024-06205-9","article-title":"Intracranial pressure monitoring in the management of acute bacterial meningitis: controversy or clinical practice","volume":"166","author":"Elmi-Terander","year":"2024","journal-title":"Acta Neurochir (Wien)"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200105033441807","article-title":"Meningococcal disease","volume":"344","author":"Rosenstein","year":"2001","journal-title":"N Engl J Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1172\/JCI104485","article-title":"Studies on the pathogenesis of meningitis. 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