Elucidating different pattern of immunoregulation in BALB/c and C57BL/6 mice and their F1 progeny.

Elucidating different pattern of immunoregulation in BALB/c and C57BL/6 mice and their F1 progeny.
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DOI:
10.1038/s41598-020-79477-7
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发表时间:
2021-01-15
期刊:
影响因子:
4.6
通讯作者:
Breloer M
Breloer M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hartmann W;Blankenhaus B;Brunn ML;Meiners J;Breloer M

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蠕虫是大型多细胞寄生虫,感染四分之一的人类。为了延长它们的生存期,蠕虫会抑制宿主的免疫反应。通过以小鼠品系特异性方式诱导调节回路来延迟圆线虫从肠道中排出:Foxp 3+调节性T细胞(Treg)的耗竭改善了抗S. BALB/c小鼠对Ratti的免疫力增强,而C57 BL/6小鼠对Ratti的免疫力无明显增强。本研究比较了BALB/c、C57 BL/6小鼠及其F1代(BALB/c × C57 BL/6)小鼠免疫调节通路的层次性。利用流式细胞术,我们发现S。Ratti通过Foxp 3 + Treg和Foxp 3 − T细胞诱导不同的抑制性检查点受体模式。表达强度在C57 BL/6中最高,在BALB/c小鼠中最低,而F1杂交具有中间表型或类似于BALB/c小鼠。在所有三种小鼠品系中,Treg亚群在感染期间扩增。与BALB/c小鼠相似,耗尽Treg减少了肠道寄生虫负荷,并增加了S.鼠感染的F1小鼠。我们的数据表明,Treg主导调节BALB/c和F1小鼠的免疫应答,而在C57 BL/6小鼠中存在多个调节层,可能弥补Treg的缺失。
Helminths are large multicellular parasites that infect one quarter of the human population. To prolong their survival, helminths suppress the immune responses of their hosts. Strongyloides ratti delays its expulsion from the gut by induction of regulatory circuits in a mouse strain-specific manner: depletion of Foxp3+ regulatory T cells (Treg) improves the anti-S. ratti immunity in BALB/c but not in C57BL/6 mice. In the current study we compare the hierarchy of immunoregulatory pathways in BALB/c, C57BL/6 mice and their F1 progeny (BALB/c × C57BL/6). Using multicolor flow cytometry, we show that S. ratti induces a distinct pattern of inhibitory checkpoint receptors by Foxp3+ Treg and Foxp3− T cells. Intensity of expression was highest in C57BL/6 and lowest in BALB/c mice, while the F1 cross had an intermediate phenotype or resembled BALB/c mice. Treg subsets expanded during infection in all three mouse strains. Similar to BALB/c mice, depletion of Treg reduced intestinal parasite burden and increased mucosal mast cell activation in S. ratti-infected F1 mice. Our data indicate that Treg dominate the regulation of immune responses in BALB/c and F1 mice, while multiple regulatory layers exist in C57BL/6 mice that may compensate for the absence of Treg.
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发表时间: 2015-02-15
影响因子: 4.4
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发表时间: 2017-05-03
影响因子: 16.6
作者:
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发表时间: 2016-09
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影响因子: --
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