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Asian Zika virus strains target CD14(+) blood monocytes and induce M2-skewed immunosuppression during pregnancy

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 immu...

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Detalles Bibliográficos
Autores principales: Foo, Suan-Sin, Chen, Weiqiang, Chan, Yen, Bowman, James W., Chang, Lin-Chun, Choi, Younho, Yoo, Ji Seung, Ge, Jianning, Cheng, Genhong, Bonnin, Alexandre, Nielsen-Saines, Karin, Brasil, Patrícia, Jung, Jae U.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5678934/
https://www.ncbi.nlm.nih.gov/pubmed/28827581
http://dx.doi.org/10.1038/s41564-017-0016-3
Descripción
Sumario: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.