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抑制 NK 细胞介导的对 PRRSV 感染的猪肺泡巨噬细胞的细胞毒性作用。

Suppression of NK cell-mediated cytotoxicity against PRRSV-infected porcine alveolar macrophages in vitro.

机构信息

Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium.

出版信息

Vet Microbiol. 2013 Jun 28;164(3-4):261-9. doi: 10.1016/j.vetmic.2013.03.001. Epub 2013 Mar 13.

DOI:10.1016/j.vetmic.2013.03.001
PMID:23522639
Abstract

The adaptive immunity against PRRSV has already been studied in depth, but only limited data are available on the innate immune responses against this pathogen. In the present study, we analyzed the interaction between porcine natural killer (NK) cells and PRRSV-infected primary porcine alveolar macrophages (PAMs), since NK cells are one of the most important components of innate immunity and PAMs are primary target cells of PRRSV infection. NK cytotoxicity assays were performed using enriched NK cells as effector cells and virus-infected or mock-inoculated PAMs as target cells. The NK cytotoxicity against PRRSV-infected PAMs was decreased starting from 6h post inoculation (hpi) till the end of the experiment (12 hpi) and was significantly lower than that against pseudorabies virus (PrV)-infected PAMs. UV-inactivated PRRSV also suppressed NK activity, but much less than infectious PRRSV. Furthermore, co-incubation with PRRSV-infected PAMs inhibited degranulation of NK cells. Finally, using the supernatant of PRRSV-infected PAMs collected at 12 hpi showed that the suppressive effect of PRRSV on NK cytotoxicity was not mediated by soluble factors. In conclusion, PRRSV-infected PAMs showed a reduced susceptibility toward NK cytotoxicity, which may represent one of the multiple evasion strategies of PRRSV.

摘要

针对 PRRSV 的适应性免疫已得到深入研究,但针对该病原体的固有免疫反应仅有有限的数据。在本研究中,我们分析了猪自然杀伤 (NK) 细胞与 PRRSV 感染的原代猪肺泡巨噬细胞 (PAMs) 之间的相互作用,因为 NK 细胞是固有免疫的最重要组成部分之一,而 PAMs 是 PRRSV 感染的主要靶细胞。使用富集的 NK 细胞作为效应细胞和病毒感染或模拟接种的 PAMs 作为靶细胞进行 NK 细胞细胞毒性测定。从接种后 6 小时 (hpi) 到实验结束 (12 hpi),针对 PRRSV 感染的 PAMs 的 NK 细胞细胞毒性逐渐降低,且显著低于针对伪狂犬病病毒 (PrV) 感染的 PAMs 的细胞毒性。紫外线灭活的 PRRSV 也抑制 NK 活性,但远低于感染性 PRRSV。此外,与 PRRSV 感染的 PAMs 共孵育会抑制 NK 细胞脱颗粒。最后,使用在 12 hpi 收集的 PRRSV 感染的 PAMs 上清液表明,PRRSV 对 NK 细胞细胞毒性的抑制作用不是由可溶性因子介导的。总之,PRRSV 感染的 PAMs 对 NK 细胞细胞毒性的敏感性降低,这可能是 PRRSV 的多种逃逸策略之一。

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