{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:36:16Z","timestamp":1792179376891,"version":"4.4.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T00:00:00Z","timestamp":1709596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012802","name":"Ragon Institute of MGH, MIT and Harvard","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012802","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011061","name":"Asia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011061","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), remains a global health burden. While M. tuberculosis is primarily a respiratory pathogen, it can spread to other organs, including the brain and meninges, causing TB meningitis (TBM). However, little is known about the immunological mechanisms that lead to differential disease across organs. Attention has focused on differences in T cell responses in the control of M. tuberculosis in the lungs, but emerging data point to a role for antibodies, as both biomarkers of disease control and as antimicrobial molecules. Given an increasing appreciation for compartmentalized antibody responses across the blood\u2013brain barrier, here we characterized the antibody profiles across the blood and brain compartments in TBM and determined whether M. tuberculosis-specific humoral immune responses differed between M. tuberculosis infection of the lung (pulmonary TB) and TBM.<\/jats:p>\n                  <jats:p>Using a high throughput systems serology approach, we deeply profiled the antibody responses against 10 different M. tuberculosis antigens, including lipoarabinomannan (LAM) and purified protein derivative (PPD), in HIV-negative adults with pulmonary TB (n = 10) versus TBM (n = 60). Antibody studies included analysis of immunoglobulin isotypes (IgG, IgM, IgA) and subclass levels (IgG1\u20134) and the capacity of M. tuberculosis-specific antibodies to bind to Fc receptors or C1q and to activate innate immune effector functions (complement and natural killer cell activation; monocyte or neutrophil phagocytosis). Machine learning methods were applied to characterize serum and CSF responses in TBM, identify prognostic factors associated with disease severity, and define the key antibody features that distinguish TBM from pulmonary TB.<\/jats:p>\n                  <jats:p>In individuals with TBM, we identified CSF-specific antibody profiles that marked a unique and compartmentalized humoral response against M. tuberculosis, characterized by an enrichment of M. tuberculosis-specific antibodies able to robustly activate complement and drive phagocytosis by monocytes and neutrophils, all of which were associated with milder TBM severity at presentation. Moreover, individuals with TBM exhibited M. tuberculosis-specific antibodies in the serum with an increased capacity to activate phagocytosis by monocytes, compared with individuals with pulmonary TB, despite having lower IgG titres and Fc\u03b3 receptor-binding capacity.<\/jats:p>\n                  <jats:p>Collectively, these data point to functionally divergent humoral responses depending on the site of infection (i.e. lungs versus brain) and demonstrate a highly compartmentalized M. tuberculosis-specific antibody response within the CSF in TBM. Moreover, our results suggest that phagocytosis- and complement-mediating antibodies may promote attenuated neuropathology and milder TBM disease.<\/jats:p>","DOI":"10.1093\/brain\/awae066","type":"journal-article","created":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T10:15:56Z","timestamp":1709201756000},"page":"3247-3260","source":"Crossref","is-referenced-by-count":24,"title":["Distinctive antibody responses to\n                    <i>Mycobacterium tuberculosis<\/i>\n                    in pulmonary and brain infection"],"prefix":"10.1093","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2548-0429","authenticated-orcid":false,"given":"Marianna","family":"Spatola","sequence":"first","affiliation":[{"name":"Ragon Institute of Mass General, MIT and Harvard , Cambridge, MA 02139 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nad\u00e8ge","family":"Nziza","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General, MIT and Harvard , Cambridge, MA 02139 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward B","family":"Irvine","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General, MIT and Harvard , Cambridge, MA 02139 , USA"},{"name":"Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deniz","family":"Cizmeci","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General, MIT and Harvard , Cambridge, MA 02139 , USA"},{"name":"Department of Biological Engineering, Massachusetts Institute of Technology , Cambridge, MA 02139 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wonyeong","family":"Jung","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General, MIT and Harvard , Cambridge, MA 02139 , USA"},{"name":"Department of Biological Engineering, Massachusetts Institute of Technology , Cambridge, MA 02139 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le Hong","family":"Van","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit, Centre for Tropical Medicine , 700000 Ho Chi Minh City , Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le Thanh Hoang","family":"Nhat","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit, Centre for Tropical Medicine , 700000 Ho Chi Minh City , Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vu Thi Ngoc","family":"Ha","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit, Centre for Tropical Medicine , 700000 Ho Chi Minh City , Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Hoan","family":"Phu","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit, Centre for Tropical Medicine , 700000 Ho Chi Minh City , Vietnam"},{"name":"Vietnam National University, School of Medicine , 700000 Ho Chi Minh City , Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dang Trung Nghia","family":"Ho","sequence":"additional","affiliation":[{"name":"Hospital for Tropical Diseases , 700000 Ho Chi Minh City , Vietnam"},{"name":"Pham Ngoc Thach University of Medicine , 700000 Ho Chi Minh City , Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy E","family":"Thwaites","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit, Centre for Tropical Medicine , 700000 Ho Chi Minh City , Vietnam"},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University , Oxford, OX3 7LG , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0050-989X","authenticated-orcid":false,"given":"Douglas A","family":"Lauffenburger","sequence":"additional","affiliation":[{"name":"Department of Biological Engineering, Massachusetts Institute of Technology , Cambridge, MA 02139 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Fortune","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Thuy Thuong","family":"Thuong","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit, Centre for Tropical Medicine , 700000 Ho Chi Minh City , Vietnam"},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University , Oxford, OX3 7LG , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galit","family":"Alter","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General, MIT and Harvard , Cambridge, MA 02139 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,3,5]]},"reference":[{"key":"2024090322143045400_awae066-B1","volume-title":"Global Tuberculosis Report 2020","author":"World Health Organization","year":"2020"},{"key":"2024090322143045400_awae066-B2","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1212\/CPJ.0000000000000023","article-title":"Tuberculous meningitis: Diagnostic and therapeutic challenges","volume":"4","author":"Chin","year":"2014","journal-title":"Neurol Clin Pract."},{"key":"2024090322143045400_awae066-B3","doi-asserted-by":"crossref","first-page":"e0000069","DOI":"10.1371\/journal.pgph.0000069","article-title":"The global burden of tuberculous meningitis in adults: A modelling study","volume":"1","author":"Dodd","year":"2021","journal-title":"PLOS Glob. 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