Cathelicidins as immunomodulators of host defence against infectious diseases

肺部疾病是导致健康不佳的最常见原因之一，占英国死亡人数的20%，其中三分之一死于传染病。超级细菌的出现是一个越来越大的挑战，迫切需要新的治疗方法和对人体自然保护机制的更多了解。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)。最初对CHDP杀灭细菌和病毒的能力进行了研究，我们发现CHDP可以通过许多方式改变炎症，调节身体对威胁和损伤的反应，以及修复系统。因此，CHDP是一种药物模板，具有杀死微生物和增强我们自然保护反应的能力。CHDP还提供了规避使超级细菌对我们目前的常规治疗产生耐药性的策略的可能性。在我最近的研究建立的基础上，我建议：1)确定CHDP关键活动所涉及的细胞通路(特别是调节呼吸道衬里细胞对感染的反应)，2)确定这些活动在预防感染方面的作用，以及3)设计新型CHDP作为潜在的治疗方法，特别关注包括流感在内的致病肺部病毒的治疗。

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.