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.

中文翻译：

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荚膜聚糖识别提供抗结核的抗体介导的免疫力。

迫切需要更好地了解与预防结核分枝杆菌感染有关的所有免疫成分，以为新型免疫疗法和结核病（TB）疫苗的开发提供信息。尽管细胞介导的免疫至关重要，但越来越多的证据支持抗体对结核病也具有保护作用。然而，保护性抗原的知识是有限的。分析来自97名美国移民的结核分枝杆菌感染各个阶段的血清，我们显示了抗结核分枝杆菌荚膜多糖阿拉伯甘露聚糖（AM）的多克隆IgG的体外和体内保护作用。使用最近开发的聚糖阵列，我们建立了在自然感染中诱导的抗AM IgG的结合特异性高度异质性，其与AM中的寡糖基序的反应性以及在卡介苗接种中和/或在对照（潜伏）与非对照（结核病）中的功能不同）结核分枝杆菌感染。我们显示，无症状但未患病的人的抗AM IgG具有保护作用，并提供数据表明IgG2和特定AM寡糖的潜在作用。我们的数据填补了人类目前对保护性抗原的知识的空白，支持结核分枝杆菌表面聚糖AM的关键作用，并表明在抗体介导的针对TB的免疫中，针对AM中特定聚糖表位的重要性。