A Functional Role for Antibodies in Tuberculosis

• Type of Material: Article
• Authors: Lenette L. Lu, Ragon Institute; Amy W. Chung, Ragon Institute; Tracy Rosebrock, Harvard School of Public Health; Musie Ghebremichael, Ragon Institute; Wen Han Yu, Ragon Institute; Patricia S. Grace, Ragon Institute; Matthew K. Schoen, Ragon Institute; Fikadu Tafesse, Ragon Institute; Constance Martin, Harvard School of Public Health; Vivian Leung, Harvard School of Public Health
• Language: English
• Date: 2016-10-06
• Publisher: Elsevier (Cell Press)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 Elsevier Inc.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.cell.2016.08.072
• Title of Journal or Parent Work: Cell
• ISSN: 0092-8674
• Volume: 167
• Issue: 2
• Start Page: 433
• End Page: 443.e14
• Grant/Funding Information: The following reagents were obtained through BEI Resources, NIAID, NIH: cell membrane, culture filtrate, cytosol protein, soluble cell wall protein and soluble protein fractions of H37RV M. tuberculosis.; CEM.NKR-CCR5 was obtained through the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH.; This work was supported by: NIH with grants R01 AI080289 and AI102660 (GA), Dr. Dan Wattendorf and DARPA BAA-11-65 (GA), Harvard University Center for AIDS Research (CFAR) P30 AI060354 (GA, SMF, TR, MG, Ragon BL3 and Imaging Core Facility), T32 AI007387 (LL), NHMRC APP1036470 (AWC), Bill and Melinda Gates Foundation CAVD (OPP1032817: Leveraging Antibody Effector Function) (GA), Pozen Family Foundation (SMF), Doris Duke Medical Research Foundation (SMF), Burroughs Wellcome Foundation (SMF) and Ragon Institute of MGH, MIT and Harvard.
• Keywords: HIGH-THROUGHPUT; MYCOBACTERIUM-TUBERCULOSIS; Cell Biology; VIRUS INFECTION; Science & Technology; Biochemistry & Molecular Biology; FC-GAMMA RECEPTORS; MONOCLONAL-ANTIBODY; MEDIATED PROTECTION; B-CELLS; DEPENDENT CELLULAR CYTOTOXICITY; HUMORAL IMMUNITY; Life Sciences & Biomedicine; EFFECTOR FUNCTIONS
• Research Categories: Health Sciences, Public Health; Health Sciences, Immunology; Biology, Microbiology

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.