Pro-resolving lipid mediators in mycobacterial infection

描述（由申请方提供）：本提案检查了促消退脂质介质、消退素、保护素和maresins在分枝杆菌发病机制中的作用。这些最近发现的脂质有效地对抗无菌性炎症，但它们在感染诱导的炎症中的作用在很大程度上尚未探索。这种探索似乎特别适用于结核病，结核病越来越被认为是一种过度和失败的炎症疾病。事实上，斑马鱼的使用揭示了脂氧素在结核病中的双重作用：过量的致病性，但在过度炎症的情况下给药时恢复耐药性。重要的是，这些斑马鱼发现的关键方面已经在人类身上得到了验证，不久将进入临床竞技场。其他促缓解介质很可能在结核病中发挥复杂作用，提供重要的治疗方法。因此，这些目标的完成不仅有助于我们理解免疫病理学如何与分枝杆菌发病机制交织在一起，而且还可能为具有免疫病理学成分的疾病提出新的治疗方法。

DESCRIPTION (provided by applicant): This proposal examines the role of the pro-resolving lipid mediators, resolvins, protectins, and maresins, in mycobacterial pathogenesis. These recently discovered lipids effectively combat sterile inflammation, but their role in infection-induced inflammation remains largely unexplored. Such an exploration seems particularly warranted for TB, which is increasingly recognized as a disease of excess as well as failed inflammation. Indeed, the use of the zebrafish has revealed a dual role for lipoxins in TB: pathogenic in excess, yet restoring resistance when administered pharmacologically in the setting of excess inflammation. Importantly, key aspects of these zebrafish findings have been validated in humans and should enter the clinical arena before long. It is very likely that the other pro-resolving mediators will play complex roles in TB that offer important therapeutic approaches. Thus, completion of these Aims will not only contribute to our understanding of how immunopathology is interwoven with mycobacterial pathogenesis, but also potentially suggest new treatments for diseases with an immunopathology component.