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暴露于不同狂犬病毒株后树突状细胞反应的比较分析。

A comparative analysis of the dendritic cell response upon exposure to different rabies virus strains.

作者信息

Kroh Keshia, Te Marvelde Merel R, van Greuningen Lars W, Laksono Brigitta M, Koopmans Marion P G, Kuiken Thijs, GeurtsvanKessel Corine H, Embregts Carmen W E

机构信息

Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.

出版信息

PLoS Negl Trop Dis. 2025 Apr 10;19(4):e0012994. doi: 10.1371/journal.pntd.0012994. eCollection 2025 Apr.

Abstract

Rabies is a viral zoonotic disease that causes over 60,000 human deaths annually worldwide. Natural infections lack a virus-specific immune response, leading to a near 100% fatality rate unless immediately treated. Rabies virus (RABV) is typically transmitted through bites from rabid dogs or other carnivores to humans and may initially interact with innate immune cells such as dendritic cells at the site of infection. This study investigates the in vitro response of human monocyte-derived dendritic cells (moDCs) exposed to two pathogenic RABV strains-silver-haired bat rabies virus (SHBRV) and dog-related rabies virus (dogRV)-and an attenuated vaccine strain (SAD P5). MoDCs were susceptible only to high doses of SHBRV and SAD P5, resulting in a more mature and migratory phenotype within the infected moDC populations. No infection was observed in moDCs exposed to dogRV. In co-culture with T cells, the presence of RABV-exposed moDCs, regardless of the strain, did not enhance T cell activation. Additionally, RABV exposure did not hinder LPS-induced moDC maturation; instead, high doses of SHBRV and SAD P5 even boosted activation levels. Overall, the findings suggest varied capabilities of RABV strains to infect and activate moDCs in vitro. However, exposure to any RABV strain did not provoke a clear antiviral state or suppression of moDC responsiveness. This lack of activation may contribute to the absence of an effective adaptive immune response in natural RABV infections.

摘要

狂犬病是一种病毒性人畜共患病,每年在全球导致6万多人死亡。自然感染缺乏针对病毒的免疫反应,除非立即治疗,否则致死率接近100%。狂犬病病毒(RABV)通常通过狂犬或其他食肉动物的咬伤传播给人类,在感染部位可能最初与先天性免疫细胞如树突状细胞相互作用。本研究调查了人单核细胞衍生树突状细胞(moDCs)对两种致病性RABV毒株——银毛蝙蝠狂犬病病毒(SHBRV)和犬相关狂犬病病毒(dogRV)以及一种减毒疫苗株(SAD P5)的体外反应。moDCs仅对高剂量的SHBRV和SAD P5敏感,在受感染的moDC群体中导致更成熟和迁移的表型。在接触dogRV的moDCs中未观察到感染。在与T细胞共培养时,无论毒株如何,暴露于RABV的moDCs的存在均未增强T细胞活化。此外,RABV暴露并未阻碍LPS诱导的moDC成熟;相反,高剂量的SHBRV和SAD P5甚至提高了活化水平。总体而言,研究结果表明RABV毒株在体外感染和激活moDCs的能力各不相同。然而,暴露于任何RABV毒株均未引发明显的抗病毒状态或抑制moDC反应性。这种缺乏活化可能导致自然RABV感染中缺乏有效的适应性免疫反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7e8/12017532/78eebd23b762/pntd.0012994.g001.jpg

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