title: Naturally produced opsonizing antibodies restrict the survival of Mycobacterium tuberculosis in human macrophages by augmenting phagosome maturation.
abstract: This study investigated the hypothesis that serum antibodies against Mycobacterium tuberculosis present in naturally infected healthy subjects of a tuberculosis (TB) endemic area could create and/or sustain the latent form of infection. All five apparently healthy Indian donors showed high titres of serum antibodies against M. tuberculosis 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 M. tuberculosis. Key enablers of macrophage microbicidal action--proinflammatory cytokines (IFN-γ and IL-6), phagosome acidification, inducible NO synthase and nitric oxide--were also significantly enhanced following antibody opsonization. Interestingly, heat-killed M. tuberculosis also elevated these mediators to the levels comparable to, if not higher than, opsonized M. tuberculosis. Results of the study support the emerging view that an efficacious vaccine against TB should, apart from targeting cell-mediated immunity, also generate 'protective' antibodies.
authors.affiliation: Division of Biochemistry, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Lucknow 226031, India.
authors.forename: Shashi Kant
authors.initials: SK
authors.lastname: Kumar
authors.affiliation: Division of Biochemistry, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Lucknow 226031, India.
authors.forename: Padam
authors.initials: P
authors.lastname: Singh
authors.affiliation: Division of Biochemistry, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Lucknow 226031, India Academy of Scientific and Innovative Research, New Delhi, India sinha.sudhir@gmail.com.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Sinha
mesh_terms: D000906:Antibodies / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D010588:Phagosomes / Q000378:metabolism*
chemical_list: D000906:Antibodies; D015850:Interleukin-6; D007371:Interferon-gamma
keywords: Mycobacterium tuberculosis; antibody opsonization; latent tuberculosis infection; phagosome maturation