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A Functional Role for Antibodies in Tuberculosis.

Authors :
Lu LL
Chung AW
Rosebrock TR
Ghebremichael M
Yu WH
Grace PS
Schoen MK
Tafesse F
Martin C
Leung V
Mahan AE
Sips M
Kumar MP
Tedesco J
Robinson H
Tkachenko E
Draghi M
Freedberg KJ
Streeck H
Suscovich TJ
Lauffenburger DA
Restrepo BI
Day C
Fortune SM
Alter G
Source :
Cell [Cell] 2016 Oct 06; Vol. 167 (2), pp. 433-443.e14. Date of Electronic Publication: 2016 Sep 22.
Publication Year :
2016

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.<br /> (Copyright © 2016 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1097-4172
Volume :
167
Issue :
2
Database :
MEDLINE
Journal :
Cell
Publication Type :
Academic Journal
Accession number :
27667685
Full Text :
https://doi.org/10.1016/j.cell.2016.08.072