**1. Introduction**

Zika virus (ZIKV) is an arthropod-borne flavivirus, considered a reemerging infectious disease as well as a neglected tropical disease [1]. Moreover, ZIKV was also classified as sexually transmitted disease (STD), since viral RNA and infectious particles were detectable in reproductive organs and others described some cases related to sexual transmission [2, 3]. Although the major concern about ZIKV infection is the intrauterine transmission [4–6].

Innate immunity during pregnancy still needs attention when some infection compromises pregnancy success. Recently, the world testified a huge public health problem during Zika virus (ZIKV) outbreak in Latin American countries [7–9], in which poor outcomes were observed firstly in Brazilian newborns from mothers infected on early pregnancy phase (1st -2nd trimester) [7, 8]. Consequences of viral infections on newborns are irreversible and public health and social costs are immensurable [10], making World Health Organization consider Zika infection a public health emergency in 2016 February [11].

Due to its neurotropic features, the infection caused by ZIKV has been evidenced [12–14], which show a correlation between clinical manifestations based on its tropism by brain neuronal cells of fetuses and neonates born from infected pregnant women, with a strong association to neurological damage, including microcephaly and other fetal neurological disorders, collectively named as Congenital Zika Syndrome (CZS) or Zika Associated with Birth Defect (ZABD) [15–18].

The immune system is composed of a set of flexible mechanisms that are fundamental to maintain homeostasis, allowing many interactions and coexistence between different populations of microorganisms and the host. The imbalance of homeostasis can be caused by a microorganism because of its pathogenic behavior. With the establishment of an active infection and consequent immune response, inflammatory mediators, produced initially, collaborate to activate cellular populations of the innate immunity, promoting antiviral and cytotoxic responses, for example. At first, these effector responses would influence the viremia resolution with the re-establishment of homeostasis. However, the loss or dysfunction of this immune response can generate a harmful environment that triggers an uncontrolled damage inflammation and consequent cell death due to a direct cytopathic effect caused by the microorganism [19].

Some studies were conducted to understand the mechanisms involved in vertical transmission. During pregnancy, the transfer of ZIKV to the placenta occurs after an infection of decidua, the placenta maternal region, since studies have shown that decidua cells are permissive to ZIKV infection and remain permissive throughout pregnancy [20, 21]. From the infection of the decidua, there are two routes by which ZIKV reaches the fetus: infection of syncytiotrophoblasts (SBTs) through capillaries containing maternal blood or infection of Extravilous Trophoblast (EVTs) by cell-to-cell propagation [4]. In vitro studies have shown that ZIKV can infect firsttrimester cytotrophoblasts CTBs and EVTs [4, 20, 21]. On the other hand, STBs are high producers of type III interferon and remain relatively resistant to viral infection throughout pregnancy, therefore, the main route hypothesis for transplacental transmission of ZIKV is that of the spread of decidua to EVTs [21, 22]. Additionally, infection of placental macrophages, the Hofbauer cells by ZIKV may contribute to both intrauterine transmission and immunomodulation [23, 24]. Further, transplacental transfer of ZIKV is more likely to occur in the pro-inflammatory environment and tolerant to placental immunity in the first trimester.

Histopathological and immunological studies in placentas have shown that infections by ZIKV lead to an increase in important inflammation markers such as TNF, CCL5, and altered vascular permeability such as metalloproteinases [25]. In addition, 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]. Therefore, there are few studies to investigate the pregnancy immunity and how the immune interface mother-to-child could contribute to infection spread with drastic

*Innate Immunity Modulation during Zika Virus Infection on Pregnancy: What We Still Need… DOI: http://dx.doi.org/10.5772/intechopen.94861*

consequences to fetus [21, 31–34]. To our knowledge, the imbalance of normal pregnancy immunity is already cause of metabolic disorders and the poor outcome is related to abortion [35–37]. Then, a viral infection can make this picture worst and tragic [8, 13, 15, 38, 39].

Like other Flaviviruses, ZIKV life cycle modulates machinery and functions of target immune host cells, making essential virus-cells interactions for pathogenesis development. Moreover, while several human and animal models' studies have argued and proved ZIKV neurotropism, there are still many answers regarding viral pathogenesis in mother and its influence the fetal neural system and persistence, and clinical outcome. In this chapter we will put together the information about innate immunity during gestation, highlighting three parts probably involved with clinical outcome: 1) interferon type III; 2) innate regulatory cells; and 3) cell death pathways modulation. Additionally, 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.
