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.

中文翻译：

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亚洲寨卡病毒株靶向CD14 +血液单核细胞，并在怀孕期间诱导M2偏斜的免疫抑制。

血液CD14 ⁺单核细胞是一线免疫调节剂，分为经典，中间或非经典子集，并在刺激后分化为M1前或M2抗炎巨噬细胞。尽管寨卡病毒（ZIKV）快速建立了病毒血症，但目标细胞和免疫反应（尤其是在怀孕期间）仍然难以捉摸。此外，尚不清楚非洲和亚洲谱系ZIKV对宿主免疫反应是否具有不同的表型影响。利用人类血液感染，我们鉴定出CD14 ⁺单核细胞是非洲或亚洲谱系ZIKV感染的主要靶标。当比较感染ZIKV的人血的免疫特征时，观察到非洲谱系ZIKV感染的经典/中间单核细胞介导的M1偏斜的炎症，而亚洲人的非经典单核细胞介导的M2偏斜的免疫抑制则相反。 ZIKV谱系感染。重要的是，孕妇血液的感染显示出对ZIKV感染的敏感性增加。特别是，亚洲血统的孕妇血液ZIKV感染导致非经典单核细胞的M2偏向免疫抑制加剧，并伴有I型干扰素信号通路的整体抑制以及与妊娠并发症相关的宿主基因的异常表达。另外30 ZIKV ⁺有症状孕妇的血清显示M2偏斜的免疫抑制细胞因子和妊娠并发症相关的纤连蛋白1水平升高。这项研究证明了血液单核细胞，特别是在怀孕期间，对不同谱系的ZIKV感染具有不同的免疫调节反应。