CD14型
免疫学
免疫抑制
寨卡病毒
怀孕
生物
免疫系统
单核细胞
病毒学
病毒
医学
遗传学
作者
Suan-Sin Foo,Weiqiang Chen,Yu-Chang Chan,James W. Bowman,Lin-Chun Chang,Younho Choi,Ji‐Seung Yoo,Jianning Ge,Genhong Cheng,Alexandre Bonnin,Karin Nielsen‐Saines,Patrícia Brasil,Jae U. Jung
出处
期刊:Nature microbiology
日期:2017-08-21
卷期号:2 (11): 1558-1570
被引量:124
标识
DOI:10.1038/s41564-017-0016-3
摘要
Blood CD14+ monocytes are frontline immunomodulators categorized into classical, intermediate or non-classical subsets, and subsequently differentiated into M1 pro- or M2 anti-inflammatory macrophages on stimulation. Although the Zika virus (ZIKV) rapidly establishes viraemia, 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 the African-lineage ZIKV infection was observed, in contrast to a non-classical monocyte-mediated M2-skewed immunosuppression by the Asian-lineage ZIKV infection. Importantly, infection of the blood of pregnant women revealed an 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 a global suppression of type I interferon-signalling pathway and an aberrant expression of host genes associated with pregnancy complications. Also, 30 ZIKV+ sera from symptomatic pregnant patients 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, on infection with different lineages of ZIKV. Both African and epidemic strains of Zika virus are shown to target CD14+ monocytes, which are more susceptible in pregnant women, but African strains are associated with inflammatory responses, and epidemic strains with immunotolerance.
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