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.

Monocytes from Uninfected Neonates Born to Trypanosoma cruzi-Infected Mothers Display Upregulated Capacity to Produce TNF-α and to Control Infection in Association with Maternally Transferred Antibodies

“…Hofbauer cells (HBC) are fetal macrophages residing in the stroma of chorionic villi (some are located close to the fetal capillaries) and the chorioamniotic membranes [ 62 , 63 ]. As they express diverse TLRs and display microbicidal activity when exposed to inflammatory stimuli, they may play a critical role for fetal protection against vertical transmission of pathogens [ 64 , 65 ]. We may thus wonder whether HBC would also be primed, similarly to monocytes circulating in neonates, thereby also contributing to protect some fetuses from congenital infection.…”

The Innate Immune Response in DENV- and CHIKV-Infected Placentas and the Consequences for the Fetuses: A Minireview

“…In addition, the decidual immunity cell population is also composed of decidual macrophages (20–25%) [ 92 ]. Decidual macrophages are the major antigen-presenting cells (APCs) at the maternal–fetal interface in early gestation; these cells are thought to also participate in vascular remodeling, trophoblastic invasion, and immune tolerance [ 96 , 97 , 98 , 99 ]. Most decidual leukocytes are recruited primarily by chemokines, such as CXCL12, CXCL8, TGF-β, and CCL2, secreted by trophoblast cells and decidual cells [ 85 , 92 ].…”

“…Once synthesized, these cytokines act in a paracrine fashion to induce a peripheral antiviral state [ 176 , 177 ]. To complete this action, different subtypes of IFN-I, including IFN beta and IFN alpha, interact with the heterodimeric IFNAR receptor (IFNAR1/FNAR 2) to trigger a JAK-STAT-mediated signaling cascade that culminates in the transcription of hundreds of genes stimulated by interferons (ISGs) that have antiviral and immunomodulatory activities [ 99 , 178 ]. ISG molecules can act by several mechanisms in order to repress viral replication, including the inhibition of virus entry into the cell, inhibition of viral protein synthesis, degradation of essential viral components, and changes in cell metabolism [ 179 , 180 ]; they even play a regulatory and immunomodulatory role [ 181 ].…”

Congenital Zika Virus Infections

“…72 ZIKV can infect placental macrophages, trophoblasts, and endothelial cells, and then enter the fetus from these cells. 73 In infected fetuses, ZIKV has been isolated from the brain and cerebrospinal fluid. 21 However, the impact of placental infection in defining the syndrome's severity has not been confirmed yet.…”