PDF(Pubmed)
Abstract：
Respiratory syncytial virus (RSV) is the most common cause of viral bronchiolitis among children worldwide, yet there is no vaccine for RSV disease. This study investigates the potential of cube and sphere-shaped cerium oxide nanoparticles (CNP) to modulate reactive oxygen (ROS) and nitrogen (RNS) species and immune cell phenotypes in the presence of RSV infection in vitro and in vivo. Cube and sphere-shaped CNP were synthesized by hydrothermal and ultrasonication methods, respectively. Physico-chemical characterization confirmed the shape of sphere and cube CNP and effect of various parameters on their particle size distribution and zeta potential. In vitro results revealed that sphere and cube CNP differentially modulated ROS and RNS levels in J774 macrophages. Specifically, cube CNP significantly reduced RSV-induced ROS levels without affecting RNS levels while sphere CNP increased RSV-induced RNS levels with minimal effect on ROS levels. Cube CNP drove an M1 phenotype in RSV-infected macrophages in vitro by increasing macrophage surface expression of CD80 and CD86 with a concomitant increase in TNFα and IL-12p70, while simultaneously decreasing M2 CD206 expression. Intranasal administration of sphere and cube-CNP were well-tolerated with no observed toxicity in BALB/c mice. Notably, cube CNP preferentially accumulated in murine alveolar macrophages and induced their activation, avoiding enhanced uptake and activation of other inflammatory cells such as neutrophils, which are associated with RSV-mediated inflammation. In conclusion, we report that sphere and cube CNP modulate macrophage polarization and innate cellular responses during RSV infection.
摘要：
呼吸道合胞病毒（RSV）是全球儿童病毒性细支气管炎的最常见原因，目前还没有针对RSV疾病的疫苗。这项研究调查了在体外和体内存在RSV感染的情况下，立方体和球形氧化铈纳米颗粒（CNP）调节活性氧（ROS）和氮（RNS）物种和免疫细胞表型的潜力。通过水热和超声方法合成了立方体和球形CNP，分别。物理化学表征证实了球形和立方体CNP的形状以及各种参数对其粒度分布和ζ电位的影响。体外结果表明，球形和立方体CNP差异调节J774巨噬细胞中的ROS和RNS水平。具体来说,立方体CNP显着降低RSV诱导的ROS水平而不影响RNS水平，而球体CNP增加RSV诱导的RNS水平，对ROS水平的影响最小。CubeCNP通过增加CD80和CD86的巨噬细胞表面表达并伴随TNFα和IL-12p70的增加，同时降低M2CD206表达，在体外驱动了RSV感染的巨噬细胞的M1表型。在BALB/c小鼠中,鼻内施用球体和立方体-CNP是良好耐受的,没有观察到毒性。值得注意的是,立方CNP优先积累在鼠肺泡巨噬细胞中并诱导其激活，避免其他炎症细胞如嗜中性粒细胞的摄取和活化增强，与RSV介导的炎症相关。总之,我们报道了球形和立方体CNP在RSV感染期间调节巨噬细胞极化和先天细胞反应。
