NK cell responses to Plasmodium infection and control of intrahepatic parasite development

NK cell responses to Plasmodium infection and control of intrahepatic parasite development
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DOI:
10.4049/jimmunol.177.2.1229
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发表时间:
2006-07-15
影响因子:
4.4
通讯作者:
Pied, Sylviane
Pied, Sylviane
中科院分区:
医学2区
文献类型:
--
作者:
Roland, Jacques;Soulard, Valerie;Pied, Sylviane

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先天免疫和适应性免疫的各种组分有助于宿主防御疟原虫感染。我们研究了NK细胞对C57 BL/6小鼠约氏疟原虫子孢子初次感染的免疫应答的贡献。我们发现,肝和脾NK细胞在感染过程中被激活,并显示出不同的表型和功能特性。肝脏NK细胞数量增加,而脾脏NK细胞数量减少。Ly 49库的表达在脾脏中被修改,但在肝脏中未被修改。脾和肝NK细胞具有不同的炎性细胞因子谱产生。此外,肝脏NK细胞在体外对YAC-1细胞和约氏疟原虫肝脏期具有细胞毒性,但对红细胞期无细胞毒性。感染小鼠脾NK细胞没有观察到这种活性。这些体外结果通过体内观察证实,Rag 2(-/-)小鼠比Rag 2(-/-)γ c(-/-)小鼠对子孢子感染更具抗性,而两种菌株在血液阶段感染后的存活率相似。因此,NK细胞参与控制疟原虫感染的早期免疫机制,主要是在红细胞前阶段。
Various components of innate and adaptive immunity contribute to host defenses against Plasmodium infection. We investigated the contribution of NK cells to the immune response to primary infection with Plasmodium yoelii sporozoites in C57BL/6 mice. We found that hepatic and splenic NK cells were activated during infection and displayed different phenotypic and functional properties. The number of hepatic NK cells increased whereas the number of splenic NK cells decreased. Expression of the Ly49 repertoire was modified in the spleen but not in the liver. Splenic and hepatic NK cells have a different inflammatory cytokines profile production. In addition, liver NK cells were cytotoxic to YAC-1 cells and P. yoelii liver stages in vitro but not to erythrocytic stages. No such activity was observed with splenic NK cells from infected mice. These in vitro results were confirmed by the in vivo observation that Rag2(-/-) mice were more resistant to sporozoite infection than Rag2(-/-) gamma c(-/-) mice, whereas survival rates were similar for the two strains following blood-stage infection. Thus, NK cells are involved in early immune mechanisms controlling Plasmodium infection, mostly at the pre-erythrocytic stage.