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

项目摘要 人类暴露于工程纳米材料（ENM）的趋势日益增加，需要跨学科的研究。 研究评估纳米材料的生物影响，并发现影响生物的基本因素， 造成这种影响。我们假设，表面和其他物理化学性质的 工程纳米材料（ENM）影响生物分子（如蛋白质）的吸附， 吸附的生物分子随后介导与生物系统的相互作用。为了验证这个假设， 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 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 对肠道中动态微生物群落的影响。我们的重点将主要放在 环境ENM和粘膜组织，如气道和肠道，其中个人将首先遇到 因此，细胞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。我们还将研究长期暴露对 组织在体内使用环境室。我们的研究包括三个具体目标 程序：（1）制备和表征冠状面ENM，用于体外和体内研究和解剖 冠状面形成与ENM理化性质的关系;（2）获得ENM的体外生物学特性， 以及由携带冠状病毒的ENM诱导的体内毒性和免疫应答概况，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的影响;以及（3） 分析携带冠状病毒的ENM对肠道微生物的影响。我们的工作将确定蛋白质 冠状动脉指纹形成的相关生物流体，发现之间的相关性 冠组成和ENM属性的集合，并揭示了细胞，组织， 和小鼠进行电晕ENM。我们将共同提供一个综合全面的观点， 纳米材料对我们环境的生物和健康影响。我们工作的长期目标是提供 有助于通过ENM的物理化学性质预测其生物影响的知识。

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.