Understanding innate immune pathway modulation using nanoparticles

了解使用纳米粒子调节先天免疫途径

• 批准号: RGPIN-2022-04060
• 负责人: Poynter, Sarah
• 金额: $ 2.04万
• 依托单位: Wilfrid Laurier University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=765041
• 关键词: Understanding; innate; immune; pathway; modulation

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.

先天性免疫系统是免疫的第一支快速反应的手臂。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，以及发出信号提醒体内的其他细胞。这是通过细胞识别病原体相关的分子模式来实现的，这些分子模式是警告细胞潜在感染的红旗。可以指示感染的一组分子是核酸，包括双链RNA和单链RNA或具有特定基序或在不寻常的细胞区室中发现的DNA。一旦被激活，由核酸识别诱导的免疫应答由信号传导分子如I型干扰素或促炎细胞因子介导;此外，这种先天性应答通知适应性免疫应答。纳米颗粒是一种很好的工具，可以进一步了解健康细胞中的基本先天免疫机制。纳米颗粒可以装载大量的核酸，产生浓缩的“炸弹”，并将其传递到细胞中。在某些情况下，这会导致细胞内免疫反应的增强。这项研究计划的长期核心目标是了解细胞对载有核酸的纳米颗粒的免疫反应。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变化？这能告诉我们先天免疫途径背后的基本机制是什么？总的来说，这个建议将为我的小说研究计划提供基础。这项研究将有助于推进我们对健康细胞中先天免疫途径的基本理解。为此，纳米颗粒将被用作一种工具，以帮助进一步梳理细胞免疫反应的复杂性，从检测到对核酸的反应。使用纳米粒子来放大核酸的刺激能力，为我们阐明免疫识别中复杂而错综复杂的信号级联提供了一条新途径。该研究项目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在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。