Cathelicidins as immunomodulators of host defence against infectious diseases

肺部疾病是最常见的疾病原因之一，占英国死亡人数的20%，其中三分之一是由于传染病。超级细菌的崛起是一个日益严峻的挑战，迫切需要新的治疗方法和对人体自然保护机制的更深入了解。我们身体早期防御系统的重要组成部分是阳离子宿主防御肽（CHDP）。最初研究它们杀死细菌和病毒的能力，我们已经发现了CHDP可以改变炎症的许多方式，调节身体对威胁和损伤的反应以及修复系统。因此，CHDP是具有杀死微生物和增强我们自然保护反应能力的药物模板。CHDP还提供了潜在的规避策略，使超级细菌对我们目前的常规治疗产生抗药性。在我最近的研究建立的基础上，我建议：1）确定参与CHDP关键活性的细胞途径（特别是调节气道衬里细胞对感染的反应），2）确定这些活性在防止感染建立中的作用，和3）设计新的CHDP作为潜在的治疗剂，特别关注治疗致病性肺病毒，包括流感。

Lung diseases are among the most common causes of ill-heath, accounting for 20% of deaths in the UK, with one third due to infectious diseases. The rise of superbugs is a ever increasing challenge, urgently requiring new treatments and a greater understanding of the body‘s natural protective mechanisms.Important components of our body‘s early defence system are cationic host-defence peptides (CHDP). Initially studied for their ability to kill bacteria and viruses, we have discovered many ways in which CHDP can alter inflammation, modulating the body‘s response to threat and damage, and the repair systems. CHDP are therefore drug templates with the capacity to kill microbes and enhance our natural protective responses. CHDP also offer the potential to circumvent the strategies that make superbugs resistant to our current conventional treatments.Building upon the foundation I have established with my recent research, I propose to: 1) determine the cellular pathways involved in the key activities of CHDP (particularly regulating the responses of airway lining cells to infection), 2) determine the role of these activities in protecting against the establishment of infection, and 3) design novel CHDP as potential therapeutics, with a particular focus on the treatment of pathogenic lung viruses, including influenza.