Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/23167
Title: Asian Zika virus strains target CD14(+) blood monocytes and induce M2-skewed immunosuppression during pregnancy
Authors: 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.
Affilliation: Department of Molecular Microbiology and Immunology. University of Southern California. Keck School of Medical. Zilkha Neurogenetic Institute.Los Angeles, CA, USA.
Department of Molecular Microbiology and Immunology. University of Southern California. Keck School of Medical. Zilkha Neurogenetic Institute.Los Angeles, CA, USA.
Division of Maternal-Fetal Medicine. Department of Obstetrics and Gynecology. University of Southern California. Keck School of Medicine. Zilkha Neurogenetic Institute. Los Angeles, CA, USA.
Department of Molecular Microbiology and Immunology. University of Southern California. Keck School of Medical. Zilkha Neurogenetic Institute.Los Angeles, CA, USA.
Department of Molecular Microbiology and Immunology. University of Southern California. Keck School of Medical. Zilkha Neurogenetic Institute.Los Angeles, CA, USA.
Department of Molecular Microbiology and Immunology. University of Southern California. Keck School of Medical. Zilkha Neurogenetic Institute.Los Angeles, CA, USA.
Department of Molecular Microbiology and Immunology. University of Southern California. Keck School of Medical. Zilkha Neurogenetic Institute.Los Angeles, CA, USA.
Department of Molecular Microbiology and Immunology. University of Southern California. Keck School of Medical. Zilkha Neurogenetic Institute.Los Angeles, CA, USA.
Department of Microbiology. Immunology and Molecular Genetics. University of California. Los Angeles, CA, USA.
Department of Cell and Neurobiology. University of Southern California. Keck School of Medicine. Zilkha Neurogenetic Institute. Los Angeles, CA, USA.
Division of Pediatric Infectious Diseases, David Geffen School of Medicine. University of California. Los Angeles. Marion Davies Children's Health Center, Los Angeles, CA, USA.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Doenças Febris Agudas. Rio de Janeiro, RJ, Brazil.
Department of Molecular Microbiology and Immunology. University of Southern California. Keck School of Medical. Zilkha Neurogenetic Institute. Los Angeles, CA, USA.
Abstract: 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.
Keywords in spanish: Zika
Pregnancy
keywords: Zika Virus
Gravidez
Issue Date: 2017
Publisher: Nature Publishing Group
Citation: SUAN-SIN, Foo etal. Asian Zika virus strains target CD14 + blood monocytes and induce M2-skewed immunosuppression during pregnancy. Nature Microbiology, v. 2, n. 11, p. 1558-1570, ago 2017
Description: Versão Preprint em acesso aberto assim como explicitado na política editorial da revista
DOI: 10.1038/s41564-017-0016-3
ISSN: 2058-5276
Copyright: restricted access
Appears in Collections:INI - Artigos de Periódicos

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