A Functional Role for Antibodies in Tuberculosis
Name
nihms864961.pdf
Size
1.22 MB
Format
Adobe PDF
Checksum (MD5)
7bda768ffeb5c9187f8421f3e3795449
Author(s)
Lu, Lenette L.
Chung, Amy W.
Rosebrock, Tracy R.
Ghebremichael, Musie
Grace, Patricia S.
Schoen, Matthew K.
Tafesse, Fikadu
Martin, Constance
Leung, Vivian
Mahan, Alison E.
Date Issued
September 2016
Journal
Cell
Publisher
Elsevier
Citation
Lu, Lenette L. et al. “A Functional Role for Antibodies in Tuberculosis.” Cell 167, 2 (October 2016): 433–443 © 2016 Elsevier Inc
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/J.CELL.2016.08.072
