1. A Functional Role for Antibodies in Tuberculosis.
- Author
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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, and Alter G
- Subjects
- Adult, Female, Glycosylation, Humans, Immunoglobulin Fc Fragments immunology, Macrophage Activation, Male, Middle Aged, Polysaccharides immunology, Protein Array Analysis, Receptors, IgG immunology, Young Adult, Antibodies, Bacterial immunology, Host-Pathogen Interactions immunology, Immunity, Humoral, Latent Tuberculosis immunology, Mycobacterium tuberculosis immunology
- 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., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
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