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活的和灭活的蜱传脑炎病毒所激活的固有免疫途径的体外特性分析

In Vitro Characterization of the Innate Immune Pathways Engaged by Live and Inactivated Tick-Borne Encephalitis Virus.

作者信息

Signorazzi Aurora, Pennings Jeroen L A, Etna Marilena P, Noya Malou, Coccia Eliana M, Huckriede Anke

机构信息

Department of Medical Microbiology & Infection Prevention, University Medical Center Groningen, University of Groningen, 9713GZ Groningen, The Netherlands.

Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), 3721MA Bilthoven, The Netherlands.

出版信息

Vaccines (Basel). 2021 Jun 17;9(6):664. doi: 10.3390/vaccines9060664.

DOI:10.3390/vaccines9060664
PMID:34204532
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8234070/
Abstract

Tick-borne encephalitis virus (TBEV) infection can lead to inflammation of the central nervous system. The disease can be effectively prevented by whole inactivated virus vaccines. Here, we investigated the innate immune profile induced in vitro by the antigen component of the vaccines, inactivated TBEV (I-TBEV), to gain insights into the mechanism of action of the TBE vaccine as compared to the live virus. To this end, we exposed human peripheral blood mononuclear cells (PBMCs) to inactivated and live TBEV and assessed cellular responses by RNA sequencing. Both inactivated and live TBEV significantly induced an interferon-dominated gene signature and an increased RIG-I-like receptor (RLR) expression. Using pathway-specific inhibitors, we assessed the involvement of pattern recognition receptors in the sensing of inactivated or live TBEV. Only RLR pathway inhibition significantly suppressed the downstream cascade induced by I-TBEV, while responses to the replicating virus were impacted by the inhibition of RIG-I-like, as well as Toll-like, receptors. Our results show that inactivated and live TBEV predominantly engaged an interferon response in our in vitro PBMC platform, and indicate RLRs as the main pattern recognition receptors involved in I-TBEV sensing.

摘要

蜱传脑炎病毒（TBEV）感染可导致中枢神经系统炎症。全灭活病毒疫苗可有效预防该疾病。在此，我们研究了疫苗抗原成分——灭活TBEV（I-TBEV）在体外诱导的先天免疫特征，以深入了解TBE疫苗与活病毒相比的作用机制。为此，我们将人外周血单核细胞（PBMC）暴露于灭活和活的TBEV，并通过RNA测序评估细胞反应。灭活和活的TBEV均显著诱导了以干扰素为主的基因特征，并增加了RIG-I样受体（RLR）的表达。使用通路特异性抑制剂，我们评估了模式识别受体在检测灭活或活TBEV中的作用。只有RLR通路抑制显著抑制了I-TBEV诱导的下游级联反应，而对复制病毒的反应则受到RIG-I样受体以及Toll样受体抑制的影响。我们的结果表明，在我们的体外PBMC平台中，灭活和活的TBEV主要引发干扰素反应，并表明RLR是参与I-TBEV检测的主要模式识别受体。

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