Thioredoxin peroxidase secreted by Echinococcus granulosus (sensu stricto) promotes the alternative activation of macrophages via PI3K/AKT/mTOR pathway
Thioredoxin peroxidase secreted by Echinococcus granulosus (sensu stricto) promotes the alternative activation of macrophages via PI3K/AKT/mTOR pathway
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细粒棘球蚴分泌的硫氧还蛋白过氧化物酶通过PI3K/AKT/mTOR途径促进巨噬细胞的选择性激活
DOI：
10.1186/s13071-019-3786-z
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发表时间：
2019-11
影响因子：
3.2
通讯作者：
Hao Wen
中科院分区：
文献类型：
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作者：
Hui Wang;Chuan-Shan Zhang;Bin-Bin Fang;Zhi-De Li;Liang Li;Xiao-Juan Bi;Wen-Ding Li;Ning Zhang;Ren-Yong Lin;Hao Wen
背景细粒棘球绦虫（Echinococcus granulosus，广义上称为细粒棘球绦虫）的幼虫在宿主体内停留时间长，但只引起轻微的炎症反应，这表明宿主炎症反应的消退是寄生虫生存的必要条件。在各种蠕虫感染中已经观察到交替激活的巨噬细胞（AAM）的募集，并且新出现的证据表明AAM对于炎症的解决至关重要。然而，AAM是否能被E.颗粒肌方法采用免疫组化法检测感染E. coli后小鼠腹腔巨噬细胞（PMs）的活化状态。通过评价表型标记的表达来分析颗粒体（狭义上）。然后用重组EgTPx（rEgTPx）及其变体（rvEgTPx）与寄生虫排泄分泌（ES）产物组合在体内和体外处理PM，并通过流式细胞术和实时PCR评估PM的活化。同时检测疟原虫感染和抗原刺激后PM中PI 3 K/AKT/mTOR通路中各种分子的磷酸化水平。颗粒肌感染，并且弗罗姆.颗粒肌（s.s.）-感染小鼠和对照小鼠。寄生虫ES产品或rEgTPx的管理诱导AAMs的招聘到腹膜和PM亚群的比例显着的倾斜，这些效果是一致的后E。颗粒肌感染ES产品或rEgTPx也诱导PM向AAM表型在体外。有趣的是，rEgTPx的这种免疫调节特性依赖于其抗氧化活性。此外，在寄生虫感染和抗原刺激后，PI 3 K/AKT/mTOR通路被激活，而AKT/mTOR抑制剂预处理可抑制该通路的激活。颗粒肌感染和ES产物，包括EgTPx，可以诱导PM募集和替代激活，至少部分地，激活了VIP 3 K/AKT/mTOR通路。这些结果表明，EgTPx诱导的AAM可能在炎症的解决中发挥关键作用，从而有利于在宿主中建立包虫囊肿。
BackgroundLarvae ofEchinococcus granulosus(sensu lato) dwell in host organs for a long time but elicit only a mild inflammatory response, which indicates that the resolution of host inflammation is necessary for parasite survival. The recruitment of alternatively activated macrophages (AAMs) has been observed in a variety of helminth infections, and emerging evidence indicates that AAMs are critical for the resolution of inflammation. However, whether AAMs can be induced byE. granulosus(s.l.) infection or thioredoxin peroxidase (TPx), one of the important molecules secreted by the parasite, remains unclear.MethodsThe activation status of peritoneal macrophages (PMs) derived from mice infected withE. granulosus(sensu stricto) was analyzed by evaluating the expression of phenotypic markers. PMs were then treatedin vivoandin vitrowith recombinant EgTPx (rEgTPx) and its variant (rvEgTPx) in combination with parasite excretory-secretory (ES) products, and the resulting activation of the PMs was evaluated by flow cytometry and real-time PCR. The phosphorylation levels of various molecules in the PI3K/AKT/mTOR pathway after parasite infection and antigen stimulation were also detected.ResultsThe expression of AAM-related genes in PMs was preferentially induced afterE. granulosus(s.s.) infection, and phenotypic differences in cell morphology were detected between PMs isolated fromE. granulosus(s.s.)-infected mice and control mice. The administration of parasite ES products or rEgTPx induced the recruitment of AAMs to the peritoneum and a notable skewing of the ratio of PM subsets, and these effects are consistent with those obtained afterE. granulosus(s.s.) infection. ES products or rEgTPx also induced PMs toward an AAM phenotypein vitro. Interestingly, this immunomodulatory property of rEgTPx was dependent on its antioxidant activity. In addition, the PI3K/AKT/mTOR pathway was activated after parasite infection and antigen stimulation, and the activation of this pathway was suppressed by pre-treatment with an AKT/mTOR inhibitor.ConclusionsThis study demonstrates thatE. granulosus(s.s.) infection and ES products, including EgTPx, can induce PM recruitment and alternative activation, at least in part,viathe PI3K/AKT/mTOR pathway. These results suggest that EgTPx-induced AAMs might play a key role in the resolution of inflammation and thereby favour the establishment of hydatid cysts in the host.
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影响因子：
5.3
作者：
通讯作者：
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影响因子：
1.5
作者：
Hewitson, James P.;Grainger, John R.;Maizels, Rick M.
通讯作者：
Maizels, Rick M.
细粒棘球蚴原头节的排泄分泌产物直接调节B10、B17和Th17细胞的分化
影响因子：
3.2
作者：
Pan W;Hao WT;Shen YJ;Li XY;Wang YJ;Sun FF;Yin JH;Zhang J;Tang RX;Cao JP;Zheng KY
通讯作者：
Zheng KY
影响因子：
16.6
作者：
Hallowell RW;Collins SL;Craig JM;Zhang Y;Oh M;Illei PB;Chan-Li Y;Vigeland CL;Mitzner W;Scott AL;Powell JD;Horton MR
通讯作者：
Horton MR
CD4+ CD25+调节T细胞体内转移后气道炎症和过度反应性的分辨率取决于白介素10。
DOI：
10.1084/jem.20051166
发表时间：
2005-12-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
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