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Cell. 2016 Oct 6;167(2):433-443.e14. doi: 10.1016/j.cell.2016.08.072. Epub 2016 Sep 22.

A Functional Role for Antibodies in Tuberculosis.

Author information

1
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
2
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Microbiology and Immunology, Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia.
3
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
4
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
5
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
6
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Biomedical Molecular Biology, Ghent University, Ghent 9000, Belgium.
7
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
8
Institute for Medical Biology, University Hospital Essen, University of Duisburg-Essen, 45141 Essen, Germany.
9
School of Public Health, University of Texas Health Houston, Brownsville, TX 78520, USA.
10
Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30307, USA; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30332, USA; South African Tuberculosis Vaccine Initiative (SATVI) and School of Child and Adolescent Health, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory, Cape Town 7925, South Africa.
11
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA. Electronic address: sfortune@hsph.harvard.edu.
12
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA. Electronic address: galter@mgh.harvard.edu.

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.

KEYWORDS:

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

PMID:
27667685
PMCID:
PMC5526202
DOI:
10.1016/j.cell.2016.08.072
[Indexed for MEDLINE]
Free PMC Article

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