Influence of the nasal microbiome on host susceptibility and response to respiratory viruses

鼻腔微生物组对宿主对呼吸道病毒的易感性和反应的影响

• 批准号: 10595400
• 负责人: Cindy Liu
• 金额: $ 75.95万
• 依托单位: GEORGE WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-17 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10595400
• 关键词: 2019-nCoV; Acute; Address; Adult; Affect; Bacteria; Child; Chronic; Coculture Techniques; Communicable Diseases; Communities; Coronavirus; Disease; Environment; Epidemiology; Epithelium; FluMist; Goals; Home; Homeostasis; Immune; Immune response; Immunology; In Vitro; Infant; Infectious Diseases Research; Inflammation; Inflammatory; Influenza; Influenza A virus; Interferons; Knowledge; Longitudinal Studies; Lower respiratory tract structure; Mission; Modeling; Mucous Membrane; Mucous body substance; Nasal cavity; Nose; Outcome; Population; Predisposition; Property; Public Health; Research; Respiratory System; Respiratory Tract Infections; Rest; Rhinovirus; Risk; Risk Reduction; Sampling; Testing; Time; United States National Institutes of Health; Upper respiratory tract; Vaccination; Variant; Viral; Viral Respiratory Tract Infection; Virus; Virus Diseases; Virus Replication; Work; airway epithelium; cytokine; disorder risk; experimental study; host-microbe interactions; improved; innovation; microbiome; microbiome composition; nasal microbiome; novel strategies; prevent; respiratory microbiome; respiratory virus; response; virology

PROJECT SUMMARY The nasal cavity has a unique microbiome, which is expected to significantly affect local immune response and in turn, susceptibility of the host to respiratory viruses. However, we know little about these potential host- microbe interactions. Our long-term goal is to elucidate how microbiome-immune interactions and dynamics within the nasal cavity affect host susceptibility to infectious and inflammatory conditions. This project’s objective is to determine natural dynamics of correlations between nasal microbiome and local immune environment and how this relationship affects host susceptibility to respiratory viral infections. Our central hypothesis is that during homeostasis, the nasal microbiome impacts local antiviral immune defenses, including epithelial integrity, mucus properties, and antiviral cytokines and specific nasal microbiome-immune environments defined by low-inflammation and high-interferon levels will confer greater natural protection against respiratory viral infections. The rationale for this project is that our knowledge regarding the adult nasal microbiome and immune environment during homeostasis is limited. Addressing this gap can immediately improve our fundamental understanding of the adult nasal cavity and inform strategies that promote naturally occurring protection against respiratory viral infections. Aim 1. Elucidate dynamics of the homeostatic nasal microbiome and immune environment in adults. We will achieve this aim by studying (i) the homeostatic nasal microbiome and innate immune profile in a cross-section of adults (n = 400) and (ii) assessing short- and long-term dynamics of adult nasal environment by selecting and following 118 adults through monthly and quarterly dense sampling over a 12-month period. Aim 2. Determine how the nasal microbiome-immune environment affects susceptibility to an intra- nasal virus challenge. We will achieve this aim by studying how pre-vaccination nasal microbiome-immune environments impact post-vaccination viral infection and replication among adult FluMist® recipients (n = 200) per year in Years 1 and 2. Aim 3. Elucidate interactions between nasal microbiome, nasal immune environment, and host susceptibility to respiratory viruses in vitro. We will achieve this aim by assessing effect of nasal microbiome composition and nasal bacterial absolute abundance on: (i) innate immune defenses and (ii) influenza A, rhinovirus, and SARS-CoV-2 infectivity using an innovative in vitro nasal microbiome-respiratory epithelial co-culture model. The proposed research is innovative because it represents a departure from the status quo by assessing how the nasal microbiome, which is ubiquitous and diverse, could affect natural immune environment. significant because it is expected to identify nasal microbiome features and immune profiles that confer natural antiviral protection, which could inform novel strategies to reduce the risk for respiratory viral infections.

项目总结 鼻腔有一个独特的微生物群，预计它会显著影响局部免疫反应。 而反过来，宿主对呼吸道病毒的易感性。然而，我们对这些潜在的宿主知之甚少- 微生物相互作用。我们的长期目标是阐明微生物-免疫相互作用和动力学 在鼻腔内影响宿主对感染和炎症条件的易感性。这个项目的 目的是确定鼻腔微生物群与局部免疫之间的相关性的自然动力学。 以及这种关系如何影响宿主对呼吸道病毒感染的易感性。我们的中央 假设在动态平衡期间，鼻部微生物群会影响局部的抗病毒免疫防御， 包括上皮完整性、粘液特性、抗病毒细胞因子和特定的鼻部微生物免疫 由低炎症和高干扰素水平定义的环境将提供更好的自然保护 对抗呼吸道病毒感染。这个项目的基本原理是，我们关于成年人的知识 鼻腔微生物群和免疫环境在动态平衡期间是有限的。解决这一差距可以 立即提高我们对成人鼻腔的基本了解，并告知策略 促进对呼吸道病毒感染的自然保护。 目的1.阐明成人鼻腔内稳态微生物群落和免疫环境的动态变化。 我们将通过研究(I)动态平衡的鼻部微生物群和先天免疫模式来实现这一目标。 成人横断面(n=400)和(Ii)评估成人鼻环境的短期和长期动态 在12个月的时间里，通过每月和每季度的密集抽样选择并跟踪118名成年人。 目的2.确定鼻腔微生物免疫环境如何影响对鼻腔内细菌的易感性 鼻腔病毒挑战。我们将通过研究疫苗接种前鼻腔微生物群免疫如何实现这一目标 环境对成年FluMist®接受者接种后病毒感染和复制的影响(n=200) 第一年和第二年每年。 目的3.阐明鼻部微生物群、鼻部免疫环境和宿主之间的相互作用 在体外对呼吸道病毒的敏感性。我们将通过评估鼻腔给药的效果来实现这一目标 微生物群组成和鼻腔细菌绝对丰度：(I)天然免疫防御和(Ii) 利用一种创新的体外鼻腔微生物群研究甲型流感、鼻病毒和SARS-CoV-2的传染性 上皮细胞共培养模型。 这项拟议的研究具有创新性，因为它通过评估 鼻腔微生物群普遍存在，种类繁多，对自然免疫环境有何影响。 具有重要意义，因为它有望识别鼻部微生物组特征和免疫图谱 天然的抗病毒保护，这可以为降低呼吸道病毒感染风险的新战略提供依据。