The Innate Defense in the Zika-Infected Placenta

Abstract

Zika virus (ZIKV) is an arthropod-borne virus that belongs to the Flaviviridae family, genus Flavivirus and was first isolated 1947 in Uganda, Africa, from the serum of a sentinel Rhesus monkey. Since its discovery, the virus was responsible for major outbreaks in several different countries, being linked to severe complications in pregnant women, neonatal birth defects and the congenital zika syndrome. Maternal-fetal transmission of ZIKV can occur in all trimesters of pregnancy, and the role of the placenta and its cells in these cases is yet to be fully understood. The decidua basalis and chorionic villi, maternal-fetal components of the placenta, contain a rich immunological infiltrate composed by Hofbauer cells, mastocytes, dendritic cells and macrophages, primary cells of the innate immune response that have a role that still needs to be better investigated in ZIKV infection. Recent studies have already described several histopathological features and the susceptibility and permissiveness of placenta cells to infection by the Zika virus. In this review, we address some of the current knowledge on the innate immune responses against ZIKV, especially in the placenta.

Keywords: Zika virus; immune response; innate immunity; placenta.

Figure 1

Schematic representation of the human maternal–fetal interface during Zika virus infection. Basal decidua with immune cells: decidual Natural Killer (dNK), maternal macrophages (dM), dendritic cells and mast cells. Chorionic villi contain trophoblast cells, mast cells, Hofbauer cells (HBC), and fetal capillaries surrounded by a layer of multinucleated syncytiotrophoblast cells. The chorionic villus is floating in the intervillous space, bathed in maternal blood. Maternal macrophages, Hofbauer cells, dendritic cells and mast cells are permissive and susceptible to ZIKV infection. Maternal macrophages and Hofbauer cells, when infected, are activated, go through hyperplasia, produce cytokines and participate in antigen presentation, and may be involved in vertical transmission. Dendritic cells participate in the immune response by presenting antigens and may be involved in vertical transmission. Mast cells, when infected, are activated, produce cytokines and may be involved in vertical transmission. Decidual Natural Killer cells produce an antiviral response by cytotoxicity.

Figure 2

Schematic representation of the interaction between the Zika virus and the IFN-I response in humans. In healthy cells, via paracrine signaling INF-I binds to IFNAR and triggers the JAK-STAT cascade that induces the transcription of ISGs. Zika virus (ZIKV) infection inhibits the transcription of ISGs by IFN-I, as the non-structural protein NS5 of ZIKV binds to STAT2 and directs its degradation in the proteasome. IFN-I has an important antiviral function due to the potential to inhibit viral replication. However, against ZIKV infection, IFN-I was associated with exacerbated response by pro-inflammatory factors and associated with placental damage.