Understanding innate immune pathway modulation using nanoparticles

先天免疫系统是快速反应的第一只免疫手臂。先天免疫系统的组成部分能够感知可能的致病威胁，并采取行动限制其有害影响，并发出信号提醒身体内的其他细胞。这是通过细胞识别病原体相关的分子模式来实现的，红色旗帜警告细胞潜在的感染。一组可以表明感染的分子是核酸，包括双链RNA和单链RNA或DNA，它们具有特定的模体或在不寻常的细胞室中发现。一旦被激活，由识别核酸引起的免疫反应是由I型干扰素或促炎细胞因子等信号分子介导的；此外，这种天生的反应通知适应性免疫反应。纳米粒子是一种极好的工具，有助于我们进一步了解健康细胞中基本的先天免疫机制。纳米粒子可以装载大量的核酸，制造出浓缩的“炸弹”，运送到细胞中。在某些情况下，这会导致细胞内的免疫反应增强。这项研究计划的长期中心目标是了解携带核酸的纳米颗粒对细胞的免疫反应。这将通过解决两个首要的研究问题来实现：为什么这种反应会有差异？关于先天免疫途径背后的基本机制，这能教会我们什么呢？总体而言，这项提议将为我的小说研究计划提供基础。这项研究将有助于促进我们对健康细胞中先天免疫途径的基本了解。为此，纳米颗粒将被用作一种工具，帮助进一步梳理细胞免疫反应的错综复杂，从检测到对核酸的反应。使用纳米粒子放大核酸的刺激能力为我们提供了一种新的途径来阐明免疫识别中涉及的复杂和错综复杂的信号级联反应。这项研究计划产生的数据对自然科学有价值，并将支持对先天免疫的进一步研究。先天免疫系统的高度保守性将允许从人类模型中收集的信息应用于其他物种，并扩大我们对所有动物免疫系统的理解。

The innate immune system is the fast acting, first arm of immunity. Components of the innate immune system are able to sense possible pathogenic threats and take action to limit their deleterious effects, as well as send out signals to alert other cells in the body. This is accomplished through cellular recognition of pathogen-associated molecular patterns, red flags to alert the cell of a potential infection. One group of molecules that can indicate an infection are nucleic acids, including double-stranded RNA and single-stranded RNA or DNA with specific motifs or found in an unusual cellular compartment. Once activated, the immune response induced by recognition of nucleic acids is mediated by signaling molecules such as type I interferon or pro-inflammatory cytokines; in addition, this innate response informs the adaptive immune response. Nanoparticles are an excellent tool to further our understanding of fundamental innate immune mechanisms in healthy cells. Nanoparticles can be loaded with large amounts of a nucleic acid, creating concentrated "bombs" to be delivered to the cells. In some cases, this leads to an enhanced immune response within the cells. The long-term central goal of this research program is to understand cellular immune responses to nanoparticles loaded with nucleic acids. This will be achieved by addressing two overarching research questions: why is there variation in this response? And what can this teach us about fundamental mechanisms behind innate immune pathways? Overall, this proposal will provide the foundation for my novel research program. This research will contribute to advancing our fundamental understanding of innate immune pathways in healthy cells. To this end, nanoparticles will be used as a tool to help further tease apart the intricacies of cellular immune responses, from detecting to responding to nucleic acids. Using nanoparticles that amplify the stimulating power of nucleic acids gives us a novel avenue for elucidating the complex and intricate signalling cascades involved in immune-recognition. The data produced by this research program are valuable to the natural sciences, and will support further research into innate immunity. The highly conserved nature of the innate immune system will allow for information gleaned in human models to be applied to other species and to broaden our understanding of the immune system of all animals.