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https://www.arca.fiocruz.br/handle/icict/63707
ASIAN ZIKA VIRUS STRAINS TARGET CD14+ BLOOD MONOCYTES AND INDUCE M2-SKEWED IMMUNOSUPPRESSION DURING PREGNANCY
https://www.arca.fiocruz.br/handle/icict/23167
Author
Affilliation
Zilkha Neurogenetic Institute. University of Southern California. Keck School of Medicine. Department of Molecular Microbiology and Immunology. Los Angeles, CA, USA.
Zilkha Neurogenetic Institute. University of Southern California. Keck School of Medicine. Department of Obstetrics and Gynecology. Division of Maternal-Fetal Medicine. Los Angeles, CA, USA.
Zilkha Neurogenetic Institute. University of Southern California. Keck School of Medicine. Department of Obstetrics and Gynecology. Division of Maternal-Fetal Medicine. Los Angeles, CA, USA.
Zilkha Neurogenetic Institute. University of Southern California. Keck School of Medicine. Department of Molecular Microbiology and Immunology. Los Angeles, CA, USA.
Zilkha Neurogenetic Institute. University of Southern California. Keck School of Medicine. Department of Molecular Microbiology and Immunology. Los Angeles, CA, USA.
Zilkha Neurogenetic Institute. University of Southern California. Keck School of Medicine. Department of Molecular Microbiology and Immunology. Los Angeles, CA, USA.
Zilkha Neurogenetic Institute. University of Southern California. Keck School of Medicine. Department of Molecular Microbiology and Immunology. Los Angeles, CA, USA.
Zilkha Neurogenetic Institute. University of Southern California. Keck School of Medicine. Department of Molecular Microbiology and Immunology. Los Angeles, CA, USA.
University of California. Immunology and Molecular Genetics. Department of Microbiology. Los Angeles, CA, USA.
Zilkha Neurogenetic Institute. University of Southern California. Keck School of Medicine. Department of Cell and Neurobiology. Los Angeles, CA, USA.
University of California. David Geffen School of Medicine. Marion Davies Children’s Health Center. Division of Pediatric Infectious Diseases. 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, Brasil.
Zilkha Neurogenetic Institute. University of Southern California. Keck School of Medicine. Department of Molecular Microbiology and Immunology. Los Angeles, CA, USA.
Zilkha Neurogenetic Institute. University of Southern California. Keck School of Medicine. Department of Obstetrics and Gynecology. Division of Maternal-Fetal Medicine. Los Angeles, CA, USA.
Zilkha Neurogenetic Institute. University of Southern California. Keck School of Medicine. Department of Obstetrics and Gynecology. Division of Maternal-Fetal Medicine. Los Angeles, CA, USA.
Zilkha Neurogenetic Institute. University of Southern California. Keck School of Medicine. Department of Molecular Microbiology and Immunology. Los Angeles, CA, USA.
Zilkha Neurogenetic Institute. University of Southern California. Keck School of Medicine. Department of Molecular Microbiology and Immunology. Los Angeles, CA, USA.
Zilkha Neurogenetic Institute. University of Southern California. Keck School of Medicine. Department of Molecular Microbiology and Immunology. Los Angeles, CA, USA.
Zilkha Neurogenetic Institute. University of Southern California. Keck School of Medicine. Department of Molecular Microbiology and Immunology. Los Angeles, CA, USA.
Zilkha Neurogenetic Institute. University of Southern California. Keck School of Medicine. Department of Molecular Microbiology and Immunology. Los Angeles, CA, USA.
University of California. Immunology and Molecular Genetics. Department of Microbiology. Los Angeles, CA, USA.
Zilkha Neurogenetic Institute. University of Southern California. Keck School of Medicine. Department of Cell and Neurobiology. Los Angeles, CA, USA.
University of California. David Geffen School of Medicine. Marion Davies Children’s Health Center. Division of Pediatric Infectious Diseases. 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, Brasil.
Zilkha Neurogenetic Institute. University of Southern California. Keck School of Medicine. Department of Molecular Microbiology and Immunology. Los Angeles, CA, USA.
Abstract
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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