PDF(Pubmed)
Abstract：
Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tb), is a major global health issue, with around 10 million new cases annually. Advances in TB immunology have improved our understanding of host signaling pathways, leading to innovative therapeutic strategies. Inflammasomes, protein complexes organized by cytosolic pattern recognition receptors (PRRs), play a crucial role in the immune response to M. tb by activating caspase 1, which matures proinflammatory cytokines IL1β and IL18. While inflammation is necessary to fight infection, excessive or dysregulated inflammation can cause tissue damage, highlighting the need for precise inflammasome regulation. Drug-resistant TB strains have spurred research into adjunctive host-directed therapies (HDTs) that target inflammasome pathways to control inflammation. Canonical and non-canonical inflammasome pathways can trigger excessive inflammation, leading to immune system exhaustion and M. tb spread. Novel HDT interventions can leverage precision medicine by tailoring treatments to individual inflammasome responses. Studies show that medicinal plant derivatives like silybin, andrographolide, and micheliolide and small molecules such as OLT1177, INF39, CY-09, JJ002, Ac-YVAD-cmk, TAK-242, and MCC950 can modulate inflammasome activation. Molecular tools like gene silencing and knockouts may also be used for severe TB cases. This review explores these strategies as potential adjunctive HDTs in fighting TB.
摘要：
结核病(TB),由结核分枝杆菌(M.tb),是一个重大的全球健康问题，每年大约有1000万新病例。结核病免疫学的进展提高了我们对宿主信号通路的理解，导致创新的治疗策略。炎性体,由胞质模式识别受体（PRR）组织的蛋白质复合物，通过激活caspase1，使促炎细胞因子IL1β和IL18成熟，在对M.tb的免疫应答中发挥关键作用。虽然炎症是对抗感染所必需的，过度或失调的炎症会导致组织损伤，强调需要精确的炎性体调节。耐药结核病菌株已经刺激了针对炎症小体途径控制炎症的辅助宿主导向疗法（HDT）的研究。规范和非规范的炎症小体途径可以引发过度的炎症，导致免疫系统衰竭和结核分枝杆菌传播。新型HDT干预措施可以通过针对个体炎症反应定制治疗方法来利用精准医学。研究表明，药用植物衍生物如水飞蓟宾，穿心莲内酯,和米色内酯和小分子，如OLT1177，INF39，CY-09，JJ002，Ac-YVAD-cmk，TAK-242和MCC950可以调节炎性体激活。基因沉默和敲除等分子工具也可用于严重的结核病病例。这篇综述探讨了这些策略作为抗击结核病的潜在辅助HDT。
