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All five apparently healthy Indian donors showed high titres of serum antibodies against<jats:italic>M. tuberculosis<\/jats:italic>cell membrane antigens, including lipoarabinomannan and alpha crystallin. Uptake and killing of bacilli by the donor macrophages was significantly enhanced following their opsonization with antibody-rich, heat-inactivated autologous sera. However, the capability to opsonize was apparent for antibodies against some and not other antigens. High-content cell imaging of infected macrophages revealed significantly enhanced colocalization of the phagosome maturation marker LAMP-1, though not of calmodulin, with antibody-opsonized compared with unopsonized<jats:italic>M. tuberculosis<\/jats:italic>. Key enablers of macrophage microbicidal action\u2014proinflammatory cytokines (IFN-<jats:italic>\u03b3<\/jats:italic>and IL-6), phagosome acidification, inducible NO synthase and nitric oxide\u2014were also significantly enhanced following antibody opsonization. Interestingly, heat-killed<jats:italic>M. tuberculosis<\/jats:italic>also elevated these mediators to the levels comparable to, if not higher than, opsonized<jats:italic>M. tuberculosis<\/jats:italic>. Results of the study support the emerging view that an efficacious vaccine against TB should, apart from targeting cell-mediated immunity, also generate \u2018protective\u2019 antibodies.<\/jats:p>","DOI":"10.1098\/rsob.150171","type":"journal-article","created":{"date-parts":[[2015,12,16]],"date-time":"2015-12-16T10:09:03Z","timestamp":1450260543000},"page":"150171","update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":52,"title":["Naturally produced opsonizing antibodies restrict the survival of<i>Mycobacterium tuberculosis<\/i>in human macrophages by augmenting phagosome maturation"],"prefix":"10.1098","volume":"5","author":[{"given":"Shashi Kant","family":"Kumar","sequence":"first","affiliation":[{"name":"Division of Biochemistry, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Lucknow 226031, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Padam","family":"Singh","sequence":"additional","affiliation":[{"name":"Division of Biochemistry, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Lucknow 226031, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudhir","family":"Sinha","sequence":"additional","affiliation":[{"name":"Division of Biochemistry, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Lucknow 226031, India"},{"name":"Academy of Scientific and Innovative Research, New Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2015,12]]},"reference":[{"key":"e_1_3_6_2_2","first-page":"56","article-title":"Fifteen year follow up of trial of BCG vaccines in south India for tuberculosis prevention","volume":"110","author":"Tuberculosis Research Centre","year":"1999","journal-title":"Indian J. 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