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鉴定感染强毒、弱毒及腐生性钩端螺旋体菌株的巨噬细胞的小转录组

Characterization of the microtranscriptome of macrophages infected with virulent, attenuated and saprophyte strains of Leptospira spp.

机构信息

Department of Support, Production and Animal Health, São Paulo State University (Unesp), School of Veterinary Medicine, Araçatuba, SP, Brazil.

Department of Clinic, Surgery and Animal Reproduction, São Paulo State University (Unesp), School of Veterinary Medicine, Araçatuba, SP, Brazil.

出版信息

PLoS Negl Trop Dis. 2018 Jul 6;12(7):e0006621. doi: 10.1371/journal.pntd.0006621. eCollection 2018 Jul.

Abstract

Leptospirosis is a bacterial zoonosis, caused by Leptospira spp., that leads to significant morbidity and mortality worldwide. Despite considerable advances, much is yet to be discovered about disease pathogenicity. The influence of epigenetic mechanisms, particularly RNA-mediated post-transcriptional regulation of host immune response has been described following a variety of bacterial infections. The current study examined the microtranscriptome of macrophages J774A.1 following an 8h infection with virulent, attenuated and saprophyte strains of Leptospira. Microarray analysis revealed that 29 miRNAs were misregulated following leptospiral infection compared to control macrophages in a strain and virulence-specific manner. Pathway analysis for targets of these differentially expressed miRNAs suggests that several processes involved in immune response could be regulated by miRNAs. Our data provides the first evidence that host miRNAs are regulated by Leptospira infection in macrophages. A number of the identified miRNA targets participate in key immune response processes. We suggest that post-transcriptional regulation by miRNAs may play a role in host response to infection in leptospirosis.

摘要

钩端螺旋体病是一种由钩端螺旋体属引起的细菌性人畜共患病,在全球范围内导致了相当高的发病率和死亡率。尽管已经取得了相当大的进展,但关于疾病发病机制的许多方面仍有待发现。在多种细菌感染后,已经描述了表观遗传机制的影响,特别是 RNA 介导的宿主免疫反应的转录后调节。本研究在 8 小时感染强毒、减毒和腐生株的钩端螺旋体后,检测了巨噬细胞 J774A.1 的微转录组。微阵列分析显示,与对照巨噬细胞相比,钩端螺旋体感染后 29 种 miRNA 的表达出现了菌株和毒力特异性的失调。对这些差异表达 miRNA 的靶标进行途径分析表明,几个参与免疫反应的过程可能受到 miRNA 的调节。我们的数据首次提供了证据,表明宿主 miRNA 受到巨噬细胞中钩端螺旋体感染的调节。许多鉴定出的 miRNA 靶标参与了关键的免疫反应过程。我们认为,miRNA 的转录后调节可能在钩端螺旋体病宿主对感染的反应中发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1806/6051669/4b387b01cdca/pntd.0006621.g001.jpg

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