Tiwari Neeraj, Kumar Vinod, Gedda Mallikarjuna Rao, Singh Ashish K, Singh Vijay K, Gannavaram Sreenivas, Singh Surya P, Singh Rakesh K
Molecular Immunology Group, Department of Biochemistry, Institute of Science, Banaras Hindu University Varanasi, India.
Department of Parasitology and Molecular Biology, Rajendra Memorial Research Institute Patna, India.
Front Microbiol. 2017 Mar 2;8:314. doi: 10.3389/fmicb.2017.00314. eCollection 2017.
The outcome of infection depends on parasite abilities to evade host immune response and its survival in hostile environment of host macrophages. Despite a wealth of gained crucial information, parasite strategies by which it dampens host macrophage functions remain poorly understood. Micro RNAs (miRNAs) are evolutionarily conserved class of endogenous 22-nucleotide small non-coding RNA gene products, described to participate in the regulation of almost every cellular process investigated so far. In this study, we identified 940 miRNAs in infected macrophages by sequencing out of which levels of 85 miRNAs were found to be consistently modified by parasite infection. Herein, we report the functional characteristics of 10 miRNAs i.e., mir-3620, mir-6385, mir-6973a, mir-6996, mir-328, mir-8113, mir-3473f, mir-763, mir-6540, and mir-1264 that were differentially but constantly regulated in infected macrophages for their role in regulation of macrophage effector functions. The target gene prediction and biological interaction analysis revealed involvement of these miRNAs in various biological processes such as apoptosis inhibition, phagocytosis, drug response, and T cell phenotypic transitions. These findings could contribute for the better understanding of macrophages dysfunction and leishmanial pathogenesis. Further, the identified miRNAs could also be used as biomarker/s in diagnosis, prognosis, and therapeutics of infection.
感染的结果取决于寄生虫逃避宿主免疫反应的能力及其在宿主巨噬细胞的恶劣环境中的存活能力。尽管已经获得了大量关键信息，但寄生虫抑制宿主巨噬细胞功能的策略仍知之甚少。微小RNA（miRNA）是一类在进化上保守的内源性22个核苷酸的小非编码RNA基因产物，据描述参与了迄今为止所研究的几乎每一个细胞过程的调控。在本研究中，我们通过测序在受感染的巨噬细胞中鉴定出940种miRNA，其中发现85种miRNA的水平因寄生虫感染而持续改变。在此，我们报告了10种miRNA的功能特性，即mir-3620、mir-6385、mir-6973a、mir-6996、mir-328、mir-8113、mir-3473f、mir-763、mir-6540和mir-1264，它们在受感染的巨噬细胞中受到差异但持续的调控，以调节巨噬细胞效应功能。靶基因预测和生物相互作用分析表明，这些miRNA参与了各种生物学过程，如凋亡抑制、吞噬作用、药物反应和T细胞表型转变。这些发现有助于更好地理解巨噬细胞功能障碍和利什曼病发病机制。此外，所鉴定的miRNA还可作为感染诊断、预后和治疗的生物标志物。
