Capsular glycan recognition provides antibody-mediated immunity against tuberculosis
Tingting Chen, … , Todd L. Lowary, Jacqueline M. Achkar
Tingting Chen, … , Todd L. Lowary, Jacqueline M. Achkar
Published January 14, 2020
Citation Information: J Clin Invest. 2020;130(4):1808-1822. https://doi.org/10.1172/JCI128459.
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Research Article Immunology Infectious disease

Capsular glycan recognition provides antibody-mediated immunity against tuberculosis

Abstract

A better understanding of all immune components involved in protecting against Mycobacterium tuberculosis infection is urgently needed to inform strategies for novel immunotherapy and tuberculosis (TB) vaccine development. Although cell-mediated immunity is critical, increasing evidence supports that antibodies also have a protective role against TB. Yet knowledge of protective antigens is limited. Analyzing sera from 97 US immigrants at various stages of M. tuberculosis infection, we showed protective in vitro and in vivo efficacy of polyclonal IgG against the M. tuberculosis capsular polysaccharide arabinomannan (AM). Using recently developed glycan arrays, we established that anti-AM IgG induced in natural infection is highly heterogeneous in its binding specificity and differs in both its reactivity to oligosaccharide motifs within AM and its functions in bacillus Calmette-Guérin vaccination and/or in controlled (latent) versus uncontrolled (TB) M. tuberculosis infection. We showed that anti-AM IgG from asymptomatic but not from diseased individuals was protective and provided data suggesting a potential role of IgG2 and specific AM oligosaccharides. Filling a gap in the current knowledge of protective antigens in humans, our data support the key role of the M. tuberculosis surface glycan AM and suggest the importance of targeting specific glycan epitopes within AM in antibody-mediated immunity against TB.

Authors

Tingting Chen, Caroline Blanc, Yanyan Liu, Elise Ishida, Sarah Singer, Jiayong Xu, Maju Joe, Elizabeth R. Jenny-Avital, John Chan, Todd L. Lowary, Jacqueline M. Achkar

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Figure 5

Coincubation of sera with Mtb with an intact capsule or AM-coupled beads reduces anti-AM IgG titers and Ab-mediated phagocytosis in THP-1 and human monocyte-derived macrophages.

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Coincubation of sera with Mtb with an intact capsule or AM-coupled beads...
(A) Anti-AM IgG titers in heat-inactivated sera (1:100) before (Non) and after depletion of Abs against the Mtb surface (H37Rv, grown without detergent) or Mtb capsular AM (coupled to beads). Sera tested were from 2 TST+IGRA+ (L) and 2 TST+IGRA– (T) subjects with high anti-AM IgG titers. No significant difference in anti-AM IgG titer reduction was observed between the 2 depletion methods (P = 0.23, paired t test). (B) Comparison of Ab effects between nondepleted (Non) and anti–Mtb surface or anti-AM Ab–depleted sera (10%) on Mtb phagocytosis by THP-1 cells. (C) Reduction of Mtb phagocytosis by human monocyte-derived macrophages (MDMs) coincubated with sera (10%) depleted of Ab against the Mtb surface (H37Rv). Columns represent mean of duplicates (circles). Because of the limited availability of cells and the focus on comparing nondepleted with antigen-specific Ab–depleted sera, FBS was not tested in duplicates.