Pro-resolving lipid mediators in mycobacterial infection

描述（由申请人提供）：本提案探讨了促溶解脂质介质，溶解蛋白，保护蛋白和蛋白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炎症，但它们在感染诱导炎症中的作用仍未被探索。这种探索似乎对结核病特别有必要，结核病越来越被认为是一种过度的疾病，也是一种炎症失败的疾病。事实上，斑马鱼实验揭示了脂毒素在结核病中的双重作用：过量致病性，但在过度炎症的情况下通过药理学给药可恢复耐药性。重要的是，这些斑马鱼研究结果的关键方面已经在人类身上得到了验证，不久之后应该会进入临床领域。其他促溶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了解免疫病理与分枝杆菌发病机制的相互作用，而且还可能为具有免疫病理成分的疾病提供新的治疗方法。

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.