Docosahexaenoic acid supplementation represses the early immune response against murine cytomegalovirus but enhances NK cell effector function.

Docosahexaenoic acid supplementation represses the early immune response against murine cytomegalovirus but enhances NK cell effector function.
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补充二十二碳六烯酸可抑制针对鼠巨细胞病毒的早期免疫反应,但增强 NK 细胞效应功能

DOI:
10.1186/s12865-022-00492-6
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发表时间:
2022-04-19
期刊:
影响因子:
3
通讯作者:
Deng, Youcai
Deng, Youcai
中科院分区:
医学4区
文献类型:
--
作者:
Wu, Shuting;Wang, Shanshan;Wang, Lili;Peng, Hongyan;Zhang, Shuju;Yang, Qinglan;Huang, Minghui;Li, Yana;Guan, Shuzhen;Jiang, Wenjuan;Zhang, Zhaohui;Bi, Qinghua;Li, Liping;Gao, Yuan;Xiong, Peiwen;Zhong, Zhaoyang;Xu, Bo;Deng, Yafei;Deng, Youcai

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二十二碳六烯酸(DHA)补充剂对几种慢性疾病有益;然而,其对免疫调节的影响仍有争议。考虑到巨细胞病毒(CMV)感染的流行,并且由于自然杀伤(NK)细胞是先天免疫的一个组成部分,对于控制CMV感染至关重要,因此本研究探讨了富含DHA的饮食对小鼠(M)CMV感染易感性和NK细胞效应器对MCMV感染的反应的影响。雄性C57 BL/6小鼠喂食对照或富含DHA的饮食3周,用MCMV感染,并在感染后指定的时间点处死。与对照组小鼠相比,DHA喂养的小鼠在感染后第7天具有较高的肝脏和脾脏病毒载量,但最终MCMV清除率不受影响。与对照组小鼠相比,感染后第7天NK细胞及其终末成熟细胞亚群(KLRG 1+和Ly 49 H + NK细胞)的总数减少,但第21天未减少。感染后第7天,DHA喂养导致脾NK细胞中IFN-γ和颗粒酶B表达增加。机制分析表明,DHA喂养小鼠的脾NK细胞具有增强的葡萄糖摄取,增加的CD 71和CD 98表达,以及比对照小鼠更高的线粒体质量。此外,DHA喂养的小鼠显示出CD 4+和CD 8 + T细胞的总数和活化水平降低。这些结果表明,DHA补充抑制CMV感染的早期反应,但通过改善线粒体活性保留NK细胞效应功能,这可能在随后的MCMV清除中发挥关键作用。在线版本包含补充材料,可通过10.1186/s12865-022-00492-6获得。
Docosahexaenoic acid (DHA) supplementation is beneficial for several chronic diseases; however, its effect on immune regulation is still debated. Given the prevalence of cytomegalovirus (CMV) infection and because natural killer (NK) cells are a component of innate immunity critical for controlling CMV infection, the current study explored the effect of a DHA-enriched diet on susceptibility to murine (M) CMV infection and the NK cell effector response to MCMV infection. Male C57BL/6 mice fed a control or DHA-enriched diet for 3 weeks were infected with MCMV and sacrificed at the indicated time points postinfection. Compared with control mice, DHA-fed mice had higher liver and spleen viral loads at day 7 postinfection, but final MCMV clearance was not affected. The total numbers of NK cells and their terminal mature cell subset (KLRG1+ and Ly49H+ NK cells) were reduced compared with those in control mice at day 7 postinfection but not day 21. DHA feeding resulted in higher IFN-γ and granzyme B expression in splenic NK cells at day 7 postinfection. A mechanistic analysis showed that the splenic NK cells of DHA-fed mice had enhanced glucose uptake, increased CD71 and CD98 expression, and higher mitochondrial mass than control mice. In addition, DHA-fed mice showed reductions in the total numbers and activation levels of CD4+ and CD8+ T cells. These results suggest that DHA supplementation represses the early response to CMV infection but preserves NK cell effector functions by improving mitochondrial activity, which may play critical roles in subsequent MCMV clearance. The online version contains supplementary material available at 10.1186/s12865-022-00492-6.
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