Asian Zika virus strains target CD14(+) blood monocytes and induce M2-skewed immunosuppression during pregnancy.
Asian Zika virus strains target CD14(+) blood monocytes and induce M2-skewed immunosuppression during pregnancy.
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DOI：
10.1038/s41564-017-0016-3
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发表时间：
2017-11
影响因子：
28.3
通讯作者：
Jung JU
中科院分区：
文献类型：
--
作者：
Foo SS;Chen W;Chan Y;Bowman JW;Chang LC;Choi Y;Yoo JS;Ge J;Cheng G;Bonnin A;Nielsen-Saines K;Brasil P;Jung JU
血CD14+单核细胞是一类一线免疫调节剂，分为经典、中间或非经典亚群，在刺激下分化为M1前或M2抗炎巨噬细胞。虽然寨卡病毒(ZIKV)迅速建立病毒血症，但靶细胞和免疫反应，特别是在怀孕期间，仍然难以捉摸。此外，非洲血统和亚洲血统的ZIKV是否对宿主免疫反应有不同的表型影响尚不清楚。利用人类血液感染，我们确定CD14+单核细胞是非洲或亚洲血统ZIKV感染的主要靶点。当比较感染ZIKV的人血的免疫图谱时，观察到非洲血统ZIKV感染的经典/中间单核细胞介导的M1偏斜炎症，而亚洲血统ZIKV感染的非经典单核细胞介导的M2偏斜免疫抑制。重要的是，孕妇血液的感染表明对寨卡病毒感染的易感性增加。具体地说，孕妇血液中的亚洲血统ZIKV感染导致非经典单核细胞M2偏斜免疫抑制加剧，同时I型干扰素信号通路受到全球抑制，与妊娠并发症相关的宿主基因异常表达。来自有症状孕妇的30份ZIKV+血清也显示M2偏斜免疫抑制细胞因子和妊娠并发症相关纤维连接蛋白-1水平升高。这项研究证明了不同ZIKV谱系感染时，血液单核细胞的免疫调节反应不同，特别是在妊娠期间。
Blood CD14+ monocytes are the frontline immunomodulators categorized into classical, intermediate or non-classical subsets, subsequently differentiating into M1 pro- or M2 anti-inflammatory macrophages upon stimulation. While Zika virus (ZIKV) rapidly establishes viremia, the target cells and immune responses, particularly during pregnancy, remain elusive. Furthermore, it is unknown whether African- and Asian-lineage ZIKV have different phenotypic impacts on host immune responses. Using human blood infection, we identified CD14+ monocytes as the primary target for African- or Asian-lineage ZIKV infection. When immunoprofiles of human blood infected with ZIKV were compared, a classical/intermediate monocyte-mediated M1-skewed inflammation by African-lineage ZIKV infection was observed, in contrast to a non-classical monocyte-mediated M2-skewed immunosuppression by Asian-lineage ZIKV infection. Importantly, infection of pregnant women’s blood revealed enhanced susceptibility to ZIKV infection. Specifically, Asian-lineage ZIKV infection of pregnant women’s blood led to an exacerbated M2-skewed immunosuppression of non-classical monocytes in conjunction with global suppression of type I interferon-signaling pathway and an aberrant expression of host genes associated with pregnancy complications. 30 ZIKV+ sera from symptomatic pregnant patients also showed elevated levels of M2-skewed immunosuppressive cytokines and pregnancy complication-associated fibronectin-1. This study demonstrates the differential immunomodulatory responses of blood monocytes, particularly during pregnancy, upon infection with different lineages of ZIKV.
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DOI：
10.1186/s40348-015-0014-6
发表时间：
2015-12
期刊：
Molecular and cellular pediatrics
影响因子：
--
作者：
Mack I;Hector A;Ballbach M;Kohlhäufl J;Fuchs KJ;Weber A;Mall MA;Hartl D
通讯作者：
Hartl D
DOI：
10.1056/nejmoa1602412
发表时间：
2016-12-15
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brasil P;Pereira JP Jr;Moreira ME;Ribeiro Nogueira RM;Damasceno L;Wakimoto M;Rabello RS;Valderramos SG;Halai UA;Salles TS;Zin AA;Horovitz D;Daltro P;Boechat M;Raja Gabaglia C;Carvalho de Sequeira P;Pilotto JH;Medialdea-Carrera R;Cotrim da Cunha D;Abreu de Carvalho LM;Pone M;Machado Siqueira A;Calvet GA;Rodrigues Baião AE;Neves ES;Nassar de Carvalho PR;Hasue RH;Marschik PB;Einspieler C;Janzen C;Cherry JD;Bispo de Filippis AM;Nielsen-Saines K
通讯作者：
Nielsen-Saines K
影响因子：
7.3
作者：
Faas MM;Spaans F;De Vos P
通讯作者：
De Vos P
影响因子：
4.3
作者：
Jaguin, Marie;Houlbert, Noemie;Lecureur, Valerie
通讯作者：
Lecureur, Valerie
影响因子：
158.5
作者：
Driggers, R. W.;Ho, C. -Y.;Vapalahti, O.
通讯作者：
Vapalahti, O.