Capsular glycan recognition provides antibody-mediated protection against tuberculosis. Capsular glycan recognition provides antibody-mediated protection against tuberculosis

Increasing evidence suggests that antibodies (Abs) can have protective roles in M. tuberculosis (Mtb) infection but knowledge of the most relevant protective antigens and epitopes in humans is limited. Using novel glycan arrays, we establish that human serum IgG induced against the M. tuberculosis (Mtb) capsular polysacharide arabinomannan (AM) in natural Mtb infection is highly heterogeneous in its binding specificity and differs in both its reactivity to oligosaccharide (OS) motifs within AM and its functions between BCG vaccination and/or controlled (latent) versus uncontrolled (TB) M. tuberculosis infection. We show that anti-AM IgG from asymptomatic but not diseased individuals is protective, and provide data suggesting a role of IgG2 and specific AM oligosaccharides. Filling a gap in the current knowledge of protective antigens in humans, our human 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. Overall design: Sera from 10 asymptomatic TST+/IGRA+ subjects and 13 symptomatic TB subjects were analyzed for anti-AM OS IgG reactivity. The anti-AM OS reactivities were then evaluated for correlations with Ab-mediated protective functions against M. tuberculosis.

越来越多的证据表明，抗体（Antibodies，Abs）在结核分枝杆菌（Mycobacterium tuberculosis，Mtb）感染中可发挥保护作用，但目前学界对人类体内相关核心保护性抗原与表位的认知仍存在局限。借助新型聚糖芯片（Glycan arrays），本研究证实：自然感染结核分枝杆菌后，针对其荚膜多糖阿拉伯甘露聚糖（Arabinomannan，AM）诱导产生的人血清免疫球蛋白G（Immunoglobulin G，IgG），其结合特异性呈现高度异质性；且该抗体在针对AM内寡糖（Oligosaccharide，OS）基序的反应性，以及卡介苗（Bacillus Calmette-Guérin，BCG）接种人群、受控（潜伏性感染）与活动性结核病（Tuberculosis，TB）感染人群间的功能特征上均存在显著差异。本研究证实，无症状感染者而非发病个体体内的抗AM IgG具有保护作用，且相关数据提示IgG2亚型与特定AM寡糖可能参与发挥保护功能。本研究填补了当前人类保护性抗原认知领域的空白，人体实验数据证实了结核分枝杆菌表面聚糖AM的核心作用，并提示在抗体介导的抗结核病免疫中，靶向AM内特定糖表位具有重要意义。
实验设计：本研究对10名结核菌素皮肤试验（Tuberculin Skin Test，TST）阳性（+）/干扰素γ释放试验（Interferon-Gamma Release Assay，IGRA）阳性（+）的无症状受试者，以及13名有症状结核病受试者的血清进行检测，以分析其抗AM寡糖IgG反应性。随后，本研究评估了抗AM寡糖反应性与抗体介导的抗结核分枝杆菌保护功能之间的相关性。