A Functional Role for Antibodies in Tuberculosis

Lenette L. Lu, Amy W. Chung, Tracy R. Rosebrock, Musie Ghebremichael, Wen Han Yu, Patricia S. Grace, Matthew K. Schoen, Fikadu Tafesse, Constance Martin, Vivian Leung, Alison E. Mahan, Magdalena Sips, Manu P. Kumar, Jacquelynne Tedesco, Hannah Robinson, Elizabeth Tkachenko, Monia Draghi, Katherine J. Freedberg, Hendrik Streeck, Todd J. SuscovichDouglas A. Lauffenburger, Blanca I. Restrepo, Cheryl Day, Sarah M. Fortune, Galit Alter

Research output: Contribution to journalArticle

174 Scopus citations

Abstract

While a third of the world carries the burden of tuberculosis, disease control has been hindered by a lack of tools, including a rapid, point-of-care diagnostic and a protective vaccine. In many infectious diseases, antibodies (Abs) are powerful biomarkers and important immune mediators. However, in Mycobacterium tuberculosis (Mtb) infection, a discriminatory or protective role for humoral immunity remains unclear. Using an unbiased antibody profiling approach, we show that individuals with latent tuberculosis infection (Ltb) and active tuberculosis disease (Atb) have distinct Mtb-specific humoral responses, such that Ltb infection is associated with unique Ab Fc functional profiles, selective binding to FcγRIII, and distinct Ab glycosylation patterns. Moreover, compared to Abs from Atb, Abs from Ltb drove enhanced phagolysosomal maturation, inflammasome activation, and, most importantly, macrophage killing of intracellular Mtb. Combined, these data point to a potential role for Fc-mediated Ab effector functions, tuned via differential glycosylation, in Mtb control.

Original languageEnglish (US)
Pages (from-to)433-443.e14
JournalCell
Volume167
Issue number2
DOIs
StatePublished - Oct 6 2016

Keywords

  • Fc-receptors
  • antibodies
  • inflammasome
  • innate immunity
  • tuberculosis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Lu, L. L., Chung, A. W., Rosebrock, T. R., Ghebremichael, M., Yu, W. H., Grace, P. S., Schoen, M. K., Tafesse, F., Martin, C., Leung, V., Mahan, A. E., Sips, M., Kumar, M. P., Tedesco, J., Robinson, H., Tkachenko, E., Draghi, M., Freedberg, K. J., Streeck, H., ... Alter, G. (2016). A Functional Role for Antibodies in Tuberculosis. Cell, 167(2), 433-443.e14. https://doi.org/10.1016/j.cell.2016.08.072