{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:00:21Z","timestamp":1780470021848,"version":"3.54.1"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Tuberculous meningitis (TBM), the most severe form of Mycobacterium tuberculosis infection, is characterized by high mortality and neurological sequelae, largely attributed to blood-brain barrier (BBB) disruption. While recent studies identified GSDMD-mediated endothelial pyroptosis as a key mechanism of inflammatory BBB damage, the full molecular landscape in TBM remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study employed an integrated multi-omics approach, combining bulk and single-cell RNA sequencing of clinical and murine datasets with experimental validation, to identify central mediators of BBB dysfunction in TBM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified and validated three genes \u2013 MARCKS, CD274 (PD-L1), and IL17RA \u2013 as significantly upregulated in TBM. Single-cell analysis of a murine TBM model demonstrated predominant MARCKS expression in CNS microglia, a finding further supported by elevated MARCKS protein levels in peripheral blood mononuclear cells from patients. However, validation in human TBM brain tissue remains warranted. Functional enrichment and correlation analyses positioned MARCKS at the nexus of inflammatory signaling and cytoskeletal regulation, showing strong associations with key effectors of the GSDMD pyroptosis pathway (CASP4, CD14, NINJ1). Our data further indicate a robust co\u2011expression pattern between MARCKS and key effectors of the GSDMD pathway (CASP5, TLR4, and CASP1), suggesting that MARCKS\u2011mediated cytoskeletal destabilization and GSDMD\u2011dependent lytic pore formation may act in concert to promote BBB disruption. Nevertheless, this proposed mechanistic interplay requires direct experimental verification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our findings nominate MARCKS as a novel mechanistic hub linking neuroinflammation to barrier pathology in TBM, revealing potential therapeutic targets for adjunctive barrier\u2011stabilizing strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1774775","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:00:44Z","timestamp":1780466444000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Co-expression of MARCKS and GSDMD pathway genes in tuberculous meningitis: a multi-omics analysis of blood-brain barrier disruption"],"prefix":"10.3389","volume":"16","author":[{"given":"Mengyu","family":"Luan","sequence":"first","affiliation":[{"name":"Beijing Chest Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyou","family":"Chen","sequence":"additional","affiliation":[{"name":"Beijing Ditan Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Lu","sequence":"additional","affiliation":[{"name":"Beijing Chest Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.nbd.2009.07.030","article-title":"Structure and function of the blood-brain barrier","volume":"37","author":"Abbott","year":"2010","journal-title":"Neurobiol. 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