Jiang Le, Belinskaya Tatyana, Zhang Zhiwen, Chan Teik-Chye, Ching Wei-Mei, Chao Chien-Chung
Viral and Rickettsial Diseases Department, Infectious Diseases Directorate, Naval Medical Research Center, Silver Spring, MD 20910, USA.
Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Microorganisms. 2020 Dec 31;9(1):80. doi: 10.3390/microorganisms9010080.
Exosomes are small extracellular vesicles that carry proteins, lipids, and nucleic acids. They are circulated in many body fluids and play an important role in intercellular communications. MicroRNAs (miRNAs), as major components of exosomes, are often regulated in many diseases including bacterial and viral infections. Functionally, exosome-carried miRNAs interact with various immune cells and affect their behavior. Little is known whether exosomal miRNAs are regulated during scrub typhus, a potentially lethal infection caused by intracellular bacteria, . In the present study, we utilized a scrub typhus mouse model and collected serum at various time points post infection. A custom quantitative PCR array covering 92 murine miRNAs was used to profile serum exosomal miRNAs. A total of 12 miRNAs were found to be significantly up- or down-regulated at least at one time point post infection when compared to uninfected animals. Further analysis identified multiple miRNAs in the let-7 family that were consistently down-regulated at early and late phase of infection. Functionally, serum exosomes isolated from infected mice displayed strong proinflammatory effect when incubated with bone marrow-derived macrophages. Our data revealed dynamic regulations of serum exosomal miRNA during scrub typhus infection, which could significantly influence host immune responses and disease outcome.
外泌体是携带蛋白质、脂质和核酸的小型细胞外囊泡。它们在多种体液中循环，在细胞间通讯中发挥重要作用。微小RNA（miRNA）作为外泌体的主要成分，在包括细菌和病毒感染在内的许多疾病中常常受到调控。在功能上，外泌体携带的miRNA与各种免疫细胞相互作用并影响其行为。对于外泌体miRNA在恙虫病（一种由细胞内细菌引起的潜在致命感染）期间是否受到调控，人们了解甚少。在本研究中，我们利用恙虫病小鼠模型，并在感染后的不同时间点收集血清。使用覆盖92种小鼠miRNA的定制定量PCR阵列对外泌体miRNA进行分析。与未感染动物相比，共发现12种miRNA在感染后的至少一个时间点显著上调或下调。进一步分析确定了let-7家族中的多种miRNA在感染的早期和晚期持续下调。在功能上，从感染小鼠中分离的血清外泌体与骨髓来源的巨噬细胞孵育时显示出强烈的促炎作用。我们的数据揭示了恙虫病感染期间血清外泌体miRNA的动态调控，这可能会显著影响宿主免疫反应和疾病结局。
