Mycobacteria have co-evolved with their hosts resulting in pathogens adept at intracellular survival. Pathogenic mycobacteria actively manipulate infected macrophages to drive granuloma formation while subverting host cell processes to create a permissive niche. Granuloma residency confers phenotypic antimicrobial resistance by physically excluding or neutralising antibiotics. Host-directed therapies (HDTs) combat infection by restoring protective immunity and reducing immunopathology independent of pathogen antimicrobial resistance status. This review covers innovative research that has discovered ‘secondary’ symptoms of infection in the granuloma stroma are actually primary drivers of infection and that relieving these stromal pathologies with HDTs benefits the host. Advances in our understanding of the relationship between tuberculosis and the host vasculature, haemostatic system and extracellular matrix reorganisation are discussed. Preclinical and clinical use of HDTs against these stromal targets are summarised.

中文翻译：

---

针对结核性肉芽肿基质的宿主定向疗法。

分枝杆菌已与其宿主共同进化，导致病原体擅长细胞内存活。致病性分枝杆菌可主动操纵感染的巨噬细胞以驱动肉芽肿形成，同时破坏宿主细胞的过程，从而创造一个允许的生态位。肉芽肿住院医师通过物理排除或中和抗生素来赋予表型抗药性。宿主定向疗法（HDTs）通过恢复保护性免疫力和减少免疫病理学而与病原体抗药性无关，从而抗击感染。这篇综述涵盖了创新的研究，这些研究发现肉芽肿基质中的“继发性”感染症状实际上是感染的主要驱动力，而通过HDT缓​​解这些基质病变对宿主有益。讨论了我们对结核与宿主脉管系统，止血系统和细胞外基质重组之间关系的理解的进展。总结了针对这些基质靶标的HDT的临床前和临床应用。