Tuberculosis (TB) infection remains a global health threat in recent decades partly due to a marked increase in the number of susceptible patients, including those with diabetes mellitus (DM) and who receive biologics. Immunity in TB infection is complex as Mycobacterium tuberculosis (MTB) is a highly adaptive pathogen and may evade the immune defense through various ways. Recent advances in TB immunity have revealed that granulomatous inflammation in TB infection is highly dynamic and the early influx of neutrophils may lead to excessive inflammation and pulmonary cavitation, which provide niches for MTB not only to survive but also to spread to other sites. Furthermore, reactive oxygen species have been found to play a crucial role among pathogenesis of TB infection in diabetics (DM-TB) through regulating inflammasome activation and the production of IL-1β, which in turn modulates the inflammatory network in TB infection, leading to dysfunctional inflammatory responses and tissue remodeling. To understand the exact immunological mechanisms underlying TB infection hence is essential for developing novel adjunctive host-directed therapy (HDT) aiming to alleviate excessive inflammation and tissue destruction and, at the same time, enhance the efficacy of currently available choices of anti-mycobacterial agents. Here we reviewed current epidemiological challenges of global TB control, novel immunological mechanisms underlying dysregulated inflammation in TB infection, especially in DM-TB, and some potential applications of adjunctive HDT in TB treatment.

中文翻译：

---

分枝杆菌如何利用现代人类免疫系统的弱点。

在最近几十年中，结核病（TB）感染仍然是全球健康威胁，部分原因是易感患者（包括患有糖尿病（DM）和接受生物制剂治疗的患者）数量显着增加。结核分枝杆菌（MTB）是一种高度适应性的病原体，可能通过各种方式逃避免疫防御，因此结核病感染的免疫力很复杂。结核病免疫力的最新进展表明，结核病感染中的肉芽肿性炎症是高度动态的，嗜中性粒细胞的早期流入可能导致过度炎症和肺气蚀，这为MTB生存和扩散提供了利基。此外，已经发现活性氧物种通过调节炎症小体激活和IL-1β的产生在糖尿病（DM-TB）的TB感染发病机理中起关键作用，进而调节TB感染中的炎症网络，导致功能异常的炎症反应和组织重塑。因此，了解结核感染的确切免疫学机制对于开发旨在减轻过度炎症和组织破坏并同时提高目前可用抗分枝杆菌药物功效的新型辅助宿主定向疗法（HDT）至关重要。 。在这里，我们回顾了当前全球结核病控制的流行病学挑战，结核病感染（尤其是DM-TB）炎症失调的新型免疫学机制，