Background

Some individuals, even when heavily exposed to an infectious tuberculosis patient, develop neither active nor latent tuberculosis infection (LTBI). This ‘early clearance’ of Mycobacterium tuberculosis is associated with a history of bacillus Calmette–Guérin (BCG) vaccination. As BCG vaccination can boost innate immune responses through a process termed ‘trained immunity’, we hypothesize that BCG-induced trained innate immunity contributes to early clearance of M. tuberculosis.

Objectives

We describe the epidemiological evidence and biological concepts of early clearance and trained immunity, and the possible relation between these two processes through BCG vaccination.

Sources

Relevant data from published reports up to November 2018 were examined in the conduct of this review.

Content

Several observational studies and one recent randomized trial support the concept that boosting innate immunity contributes to protection against M. tuberculosis infection, with BCG vaccination providing approximately 50% protection. The molecular mechanisms mediating early clearance remain largely unknown, but we propose that trained immunity, characterized by epigenetic and metabolic reprogramming of innate immune cells such as monocytes or macrophages, is at least partially responsible for eliminating the mycobacteria and inducing early clearance.

Implications

Future studies should examine if BCG revaccination increases early clearance of M. tuberculosis through induction of trained immunity. Epigenetic or metabolic modulation may further boost BCG-induced trained innate immunity to promote tuberculosis prevention. New tuberculosis vaccine candidates should also be examined for their capacity to improve protection against M. tuberculosis infection and induce trained immunity.

中文翻译：

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训练有素的先天免疫力和对结核分枝杆菌感染的抵抗力

背景

有些人即使严重接触传染性结核病患者，也不会发展为活动性或潜伏性结核感染（LTBI）。结核分枝杆菌的这种“早期清除”与卡介苗的接种史有关。由于BCG疫苗接种可以通过称为“训练后的免疫力”的过程增强先天免疫应答，因此我们假设BCG诱导的训练后的先天免疫力有助于结核分枝杆菌的早期清除。

目标

我们描述了早期清除和训练有素的免疫力的流行病学证据和生物学概念，以及通过BCG疫苗接种在这两个过程之间的可能关系。

资料来源

审查过程中检查了截至2018年11月的已发布报告的相关数据。

内容

几项观察性研究和一项近期的随机试验支持这一观念，即提高先天免疫力有助于抵抗结核分枝杆菌感染，卡介苗接种可提供约50％的保护。介导早期清除的分子机制仍然是未知的，但我们建议以先天免疫细胞（如单核细胞或巨噬细胞）的表观遗传和代谢重编程为特征的训练有素的免疫至少部分负责消除分枝杆菌并诱导早期清除。

含意

未来的研究应检查卡介苗重新接种是否通过诱导训练有素的免疫力提高结核分枝杆菌的早期清除率。表观遗传或代谢调节可进一步增强BCG诱导的训练性先天免疫力，从而促进结核病的预防。还应检查新的结核病疫苗候选者改善对结核分枝杆菌感染的保护并诱导训练有素的免疫力的能力。