Foxp3(+) regulatory T cell expansion required for sustaining pregnancy compromises host defense against prenatal bacterial pathogens.
Foxp3(+) regulatory T cell expansion required for sustaining pregnancy compromises host defense against prenatal bacterial pathogens.
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DOI：
10.1016/j.chom.2011.06.005
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发表时间：
2011-07-21
影响因子：
30.3
通讯作者：
Way SS
中科院分区：
文献类型：
--
作者：
Rowe JH;Ertelt JM;Aguilera MN;Farrar MA;Way SS
虽然妊娠赋予独特的易感性感染，妊娠相关的免疫缺陷，削弱宿主防御仍然在很大程度上不确定。在此，我们证明了免疫抑制Foxp 3+调节性T细胞（TCRs）的扩增，其在妊娠期间生理上发生或在转基因小鼠中实验诱导时，各自引起对产前病原体（包括李斯特菌和沙门氏菌属）的易感性增强。相反，Treg消融一致降低了感染易感性。然而，重要的是，母体T细胞的持续扩增对于维持对发育中的胎儿的免疫耐受性是必不可少的，因为即使是部分瞬时消融表达Foxp 3的细胞也会破坏母体对胎儿抗原的耐受性并引发胎儿吸收。有趣的是，Foxp 3细胞内在缺陷的免疫抑制细胞因子IL-10单独足以推翻Treg介导的感染易感性，而IL-10是维持妊娠不必要的。因此，维持妊娠所需的母体Treg扩增在赋予产前感染易感性的宿主防御中产生天然存在的漏洞。
Although pregnancy confers unique susceptibility to infection, the pregnancy-associated immune defects that erode host defense remain largely undefined. Herein, we demonstrate that expansion of immune-suppressive Foxp3+ regulatory T cells (Tregs) which occurs physiologically during pregnancy or when experimentally induced in transgenic mice each caused enhanced susceptibility to prenatal pathogens including Listeria and Salmonella species. Reciprocally, infection susceptibility was uniformly reduced with Treg-ablation. Importantly however, the sustained expansion of maternal Tregs was essential for maintaining immune tolerance to the developing fetus because even partial transient ablation of Foxp3-expressing cells fractured maternal tolerance to fetal antigen and triggered fetal resorption. Interestingly, Foxp3 cell-intrinsic defects in the immune suppressive cytokine IL-10 alone were sufficient to override Treg-mediated infection susceptibility, while IL-10 was non-essential for sustaining pregnancy. Thus, maternal Treg expansion required for sustaining pregnancy creates naturally occurring holes in host defense that confers prenatal infection susceptibility.
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影响因子：
32.4
作者：
Fontenot, JD;Rasmussen, JP;Rudensky, AY
通讯作者：
Rudensky, AY
影响因子：
30.5
作者：
Fallarino, F;Grohmann, U;Puccetti, P
通讯作者：
Puccetti, P
影响因子：
4.6
作者：
Gregg, R;Smith, CM;Moss, PA
通讯作者：
Moss, PA
影响因子：
4.4
作者：
Burchill, MA;Goetz, CA;Farrar, MA
通讯作者：
Farrar, MA
DOI：
10.1084/jem.20081811
发表时间：
2009-02-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Friedline RH;Brown DS;Nguyen H;Kornfeld H;Lee J;Zhang Y;Appleby M;Der SD;Kang J;Chambers CA
通讯作者：
Chambers CA