Myeloid-derived suppressor cells are key players in the resolution of inflammation during a model of acute infection
Myeloid-derived suppressor cells are key players in the resolution of inflammation during a model of acute infection
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DOI：
10.1002/eji.201343606
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发表时间：
2014-01-01
影响因子：
5.4
通讯作者：
Gea, Susana
中科院分区：
文献类型：
--
作者：
Arocena, Alfredo R.;Onofrio, Luisina I.;Gea, Susana
髓源性抑制细胞（MDSC）是免疫抑制网络中的关键参与者。在急性感染查加斯病的病原体克氏锥虫期间，BALB/c小鼠比C57 BL/6（B6）小鼠表现出更少的炎症和更好的存活率。在这项比较研究中，我们发现感染的BALB/c小鼠的脾脏和肝脏中的MDSC数量高于感染的B6小鼠。两个主要的MDSCs亚群的分析显示，更多的粒细胞在脾脏和肝脏的BALB/c小鼠相比，在B6小鼠。此外，从感染的BALB/c小鼠纯化的脾MDSC抑制ConA诱导的脾细胞增殖。机制研究表明，ROS和一氧化氮参与MDSC的抑制活性，与未感染的对照相比，受感染的CD 8 +T细胞的表面硝化数量更高。NADPH氧化酶p47 phox亚基和p-STAT 3在MDSC中发生上调，感染的IL-6 KO小鼠显示MDSC募集较少，存活受损。值得注意的是，MDSC的体内消耗导致IL-6、IFN-γ和Th 17应答的产生增加，寄生虫血症和死亡率非常高。这些发现证明了MDSC作为T过程中炎症的重要调节因子的新方面。克鲁兹感染。
Myeloid‐derived suppressor cells (MDSCs) are key players in the immune suppressive network. During acute infection with the causative agent of Chagas disease,Trypanosoma cruzi, BALB/c mice show less inflammation and better survival than C57BL/6 (B6) mice. In this comparative study, we found a higher number of MDSCs in the spleens and livers of infected BALB/c mice compared with infected B6 mice. An analysis of the two major MDSCs subsets revealed a greater number of granulocytic cells in the spleens and livers of BALB/c mice when compared with that in B6 mice. Moreover, splenic MDSCs purified from infected BALB/c mice inhibited ConA‐induced splenocyte proliferation. Mechanistic studies demonstrated that ROS and nitric oxide were involved in the suppressive activity of MDSCs, with a higher number of infected CD8+T cells suffering surface‐nitration compared to uninfected controls. An upregulation of NADPH oxidase p47 phox subunit and p‐STAT3 occurred in MDSCs and infected IL‐6 KO mice showed less recruitment of MDSCs and impaired survival. Remarkably, in vivo depletion of MDSCs led to increased production of IL‐6, IFN‐γ, and a Th17 response with very high parasitemia and mortality. These findings demonstrate a new facet of MDSCs as crucial regulators of inflammation duringT. cruziinfection.