Abstract
Zika virus (ZIKV), an arthropod-borne flavivirus, was classified as reemerging infectious disease and included as neglected tropical disease. During the recent ZIKV outbreak in South America, it has been demonstrated that ZIKV infection during pregnancy is strongly associated with fetal loss, malformations and neurological disorders in newborns. Despite the first line of host immune defense is related to innate immunity activation, the immunological homeostasis is essential for pregnancy success. Although the dynamic changes in maternal-fetal immunity is not completely understood and poorly investigated, the knowledge of immune responses during gestation is very important for infectious disease prevention and control, as ZIKV. Here, we put together more and new information about the innate immunity during gestation, highlighting three parts probably involved with clinical outcome and/or not well explored in literature: 1) type III interferon; 2) innate regulatory cells; and 3) cell death pathways modulation. Additionally, we will be focused on discussing how the dynamic responses of innate immune system during pregnancy and its effects in newborns, could be modulated by ZIKV, as well as how efforts on development of new/old drugs and vaccines could be effective for ZIKV prevention and control to provide a successful pregnancy.
Highlights
Zika virus (ZIKV) is an arthropod-borne flavivirus, considered a reemerging infectious disease as well as a neglected tropical disease [1]
In the acute ZIKV infection during pregnancy, macrophages and dendritic cells are involved in inflammatory cytokines production, in which CARD9 expression, an important regulator of caspase activity playing an important role in cell apoptosis regulation, is elevated allowing that pattern recognition receptors (PRR) induce pro-inflammatory cytokines cascade, as the first step on Congenital Zika Syndrome (CZS), as suggested [67]
Considering the normal pregnancy, the innate immunity balance is conduct by downregulation of effector T cells and NK cells leading by innate regulatory cells (MDSC) and upregulation of pro-inflammatory cytokines
Summary
Zika virus (ZIKV) is an arthropod-borne flavivirus, considered a reemerging infectious disease as well as a neglected tropical disease [1]. STBs are high producers of type III interferon and remain relatively resistant to viral infection throughout pregnancy, the main route hypothesis for transplacental transmission of ZIKV is that of the spread of decidua to EVTs [21, 22]. In vitro experiments demonstrate that trophoblastic cells become progressively more resistant to infection by ZIKV during pregnancy, partly through the secretion of IFNs [26] In this context, a lot of efforts were raised to provide funds to deeply investigate how to avoid another spread of Zika virus infection, as well as drugs tests and vaccine development based on viral proteins, DNA vaccines, Virus Like Particles (VLP), chimeric viruses, among other strategies [27–30]. We will focus on discussing how the dynamic responses of innate immune system during pregnancy and its effects in newborns, could be modulated by ZIKV, as well as how efforts on development of new/old drugs and vaccines could be effective to help pregnancy success
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