ArticleResearch square2026
Host-directed treatments for tuberculous meningitis: A multi-platform approach across mouse and human models.
Sanjay Jain, Carlos Ruiz Gonzalez, Medha Singh, Yuderleys Masias Leon, Xueyi Chen, Mona Sarhan, Yazmin Martinez-Martinez, Shruti Patel, Madelynn Shambles, Andres Villabona-Rueda and 11 more
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In one paragraphArticle in Research square, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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2 · The registryThe trial behind it
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4 · The recordCorrections and comments
5 · Who and what moneyAuthors and funding
21 authors.
Carlos Ruiz GonzalezCincinnati Children's Hospital Medical Center.
Medha SinghCincinnati Children's Hospital Medical Center.
Yuderleys Masias LeonCincinnati Children's Hospital Medical Center.
Mona SarhanCincinnati Children's Hospital Medical Center.
Shruti PatelJohns Hopkins University School of Medicine.
Madelynn ShamblesJohns Hopkins University School of Medicine.
Andres Villabona-RuedaMiller School of Medicine, University of Miami.
Kadia LissitJohns Hopkins University School of Medicine.
David TweedieNational Institutes of Health.
Michael ScerbaNational Institutes of Health.
William BishaiJohns Hopkins University, School of Medicine, Department of Medicine, Center for Tuberculosis Research, Baltimore.ORCID 0000-0002-8734-4118 Dmitri ArtemovJohns Hopkins University School of Medicine.
Franco D'AlessioMiller School of Medicine, University of Miami.
Richard HafnerNational Institutes of Health.
Nigel GreigNIA.
Maura ManionNational Institute of Allergy and Infectious Diseases.
Funding
Research Education ComponentP30AG066507 · NIA · JOHNS HOPKINS UNIVERSITY · PI Corinne Pettigrew · 2020 to 2026
$29.3MPreclinical modeling to study Tuberculous MeningitisR01AI145435 · NIAID · JOHNS HOPKINS UNIVERSITY · PI JAIN, SANJAY · 2020 to 2024
$4.0MMeasuring Intralesional Drug Exposures in Cavitary TB using Noninvasive In Vivo PET ImagingR01AI153349 · NIAID · JOHNS HOPKINS UNIVERSITY · PI JAIN, SANJAY · 2020 to 2024
$3.8MTargeted cell-depleting immunotherapy for TB and HIVR01AI152688 · NIAID · JOHNS HOPKINS UNIVERSITY · PI BISHAI, WILLIAM RAMSES · 2020 to 2024
$3.4M7T Cryogen-Free Preclinical MRI for small animals to study infectious diseases in BSL-3 containmentS10OD030381 · OD · JOHNS HOPKINS UNIVERSITY · PI JAIN, SANJAY · 2022 to 2022
$1.7MPro-apoptotic Drugs as Host-Directed Treatments for Pulmonary Tuberculosis”R01AI190038 · NIAID · JOHNS HOPKINS UNIVERSITY · PI Sanjay K Jain · 2025 to 2026
$1.6MPro-apoptotic Drugs as Host-Directed Treatments for Pulmonary TuberculosisR56AI179012 · NIAID · JOHNS HOPKINS UNIVERSITY · PI JAIN, SANJAY · 2024 to 2024
$818kNIAID NIH HHS R01 AI145435NIAID NIH HHS R01 AI152688NIAID NIH HHS R01 AI153349NIAID NIH HHS R01 AI190038NIAID NIH HHS R56 AI179012NIA NIH HHS P30 AG066507NIH HHS S10 OD030381
6 · The paper itselfAbstract
Tuberculous meningitis (TB meningitis) is a major cause of death and neurological deficit despite recommended antibiotic and corticosteroid treatments, primarily due to dysregulated neuroinflammation. Here, we investigate a diverse panel of 12 immunomodulatory drugs as host-directed treatments (HDTs) for TB meningitis utilizing a cross-species framework comprising studies in a mouse model of TB meningitis with clinical endpoints, and parallel mechanistic studies in a newly developed immune-vascularized human brain organoid model of TB meningitis and peripheral blood mononuclear cells (PBMCs) from patients with TB meningitis. We identify new HDTs that outperform the current standard of care by reducing mortality and neurological deficits in mice via suppression of neuroinflammation. Importantly, these HDTs significantly reduce microglial activation in
Identifiers
PMID41836508
PMCPMC12980363
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