CD1d AS A NOVEL REGULATOR OF INNATE IMMUNITY

Toll样受体是一组在免疫系统中发挥关键作用的蛋白质，它是识别病毒或细菌等病原体的第一屏障。TLRs对这些病原体的识别启动了免疫细胞的级联激活，最终导致病原体的消除。然而，在自身免疫性疾病或败血症的情况下，TLRs的不适当激活可能对健康有害。因此，了解控制TLRs激活的过程对于调节保护性和致病性免疫反应之间的平衡至关重要。最近的研究表明，脂类胆固醇是TLR信号的关键调节因子。这表明，控制胆固醇合成途径(例如，使用他汀类药物)可能是增强或抑制免疫反应的工具。然而，调节免疫细胞激活和胆固醇代谢之间的串扰的详细过程仍不清楚。这项建议的主要目的是了解连接胆固醇代谢和TLR反应的途径。我们将深入研究控制TLR激活的途径，调查它们与胆固醇代谢的关系，并评估它们在细菌感染期间的功能。了解调节TLR激活的机制将有助于设计更好的预防和治疗传染病和炎症性疾病的策略。

Toll-like receptors (TLR) are a group of proteins that play a key role in the immune system by functioning as a first barrier for the recognition of pathogens such as virus or bacteria. The recognition of such pathogens by TLRs initiates a cascade of activation of immune cells that ultimately leads to pathogen elimination. However, the inappropriate activation of TLRs can be detrimental for health as in the case of autoimmune diseases or sepsis. Thus, understanding the processes that control the activation of TLRs is critical to modulate the balance between protective and pathogenic immune responses. Recent studies have proposed a role for the lipid cholesterol as a key regulator of TLR signalling. This suggests that controlling the cholesterol synthesis pathways (for instance by using statins) could be a tool to potentiate or dampen immune responses. However, the detailed processes regulating the crosstalk between immune cell activation and cholesterol metabolism remain unclear. The main aim of this proposal is to understand the pathways that link cholesterol metabolism and TLR responses. We will study in-depth the pathways that control TLR activation, investigate how they relate to cholesterol metabolism and evaluate their function during bacterial infection. Understanding the mechanisms regulating TLR activation will help design better strategies for prevention and treatment of infectious and inflammatory diseases.