Nano-response: Immune stimulation, microbiome perturbation, and impacts from protein corona

项目总结 人类接触工程纳米材料(ENM)的趋势越来越大，这需要跨学科的研究 研究评估纳米材料的生物影响，并发现 造成这样的影响。我们假设，表面和其他物理化学性质 工程纳米材料(ENM)影响蛋白质等生物分子的吸附，而由 吸附的生物分子随后调节与生物系统的相互作用。为了检验这一假设， 我们由化学家、免疫学家和环境工程师组成的团队进行的综合研究将看起来 这些相互作用对组织中炎症和免疫反应的激活的影响，以及 对肠道内动态微生物群落的影响。我们的重点将主要放在 环境中的ENM和粘膜组织，如呼吸道和肠道，在这些地方个人将首先遇到 因此，细胞间的相互作用也将集中在肺泡巨噬细胞和上皮细胞上， 肠上皮和粘膜免疫组织。我们还将研究长期接触对人体健康的影响 在活体组织中使用环境舱。我们的研究包含三个具体目标 计划：(1)体外和体内研究和解剖所需的具有电晕作用的ENM的制备和表征 电晕形成与ENM理化性质的关系：(2)体外获取 以及携带电晕的ENM诱导的体内毒性和免疫应答情况，并确定其影响 亚慢性和慢性暴露于吸入ENM对细胞和组织对抗原的反应；及(3) 分析携带电晕的环氧乙烷对肠道微生物群的影响。我们的工作将确定这种蛋白质 在暴露相关的生物流体中形成的冠状病毒的指纹，发现 电晕成分和ENM特性的集合，并揭示来自细胞、组织、 并将老鼠送到携带日冕的环状病毒上。我们将共同提供一个完整和全面的观点 纳米材料在我们环境中的生物和健康影响。我们工作的长期目标是实现 可通过其物理化学性质帮助预测ENMS的生物影响的知识。

PROJECT SUMMARY The increasing trend in human exposure to engineered nanomaterials (ENMs) calls for interdisciplinary researches to assess the biological impacts from nanomaterials and discover the fundamental factors that contribute to such impacts. We hypothesize that, the surface and other physicochemical properties of engineered nanomaterials (ENMs) affect adsorption of biomolecules like proteins, and the corona formed by the adsorbed biomolecules subsequently mediate interaction with biological systems. To test this hypothesis, our integrated study carried out by a team of chemists, immunologists, and environmental engineers will look at the effects of these interactions on activation of inflammatory and immune responses in tissues, as well as the effect on the dynamic microbial community in the gut. Our focus will be mainly on the interactions between environmental ENMs and mucosal tissues such as the airways and gut, where individuals will first encounter the ENMs; consequently, cellular interactions will also focus on lung alveolar macrophages and epithelium, intestinal epithelium, and mucosal immune tissues. We will also study the effects of chronic exposure on tissues in vivo using an environmental chamber. Three specific aims are incorporated into our research program: (1) To generate and characterize the corona-bearing ENMs for in vitro and in vivo study and dissect the relationship between corona formation and ENM's physicochemical properties; (2) To acquire the in vitro and in vivo toxicity and immune response profiles induced by corona-carrying ENMs and determine the impact of sub-chronic and chronic exposure to inhaled ENMs on cell and tissue responses to antigen; and (3) To analyze impacts from the corona-carrying ENMs on gut microbiomes. Our work will identify the protein fingerprints of the coronas formed in the exposure-relevant biological fluids, discover the correlation between corona composition and a collection of ENM properties, and reveal the biological responses from cells, tissues, and mice to the corona-carrying ENMs. Together, we will provide an integrated and comprehensive view of the biological and health impacts of nanomaterials in our environment. The long term goal of our work is to deliver knowledge that could help to predict the biological impacts of ENMs by their physicochemical properties.