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

Abstract

Dengue virus (DENV) and chikungunya (CHIKV) are arthropod-borne viruses belonging to the Flaviviridae and Togaviridae families, respectively. Infection by both viruses can lead to a mild indistinct fever or even lead to more severe forms of the diseases, which are characterized by a generalized inflammatory state and multiorgan involvement. Infected mothers are considered a high-risk group due to their immunosuppressed state and the possibility of vertical transmission. Thereby, infection by arboviruses during pregnancy portrays a major public health concern, especially in countries where epidemics of both diseases are regular and public health policies are left aside. Placental involvement during both infections has been already described and the presence of either DENV or CHIKV has been observed in constituent cells of the placenta. In spite of that, there is little knowledge regarding the intrinsic earlier immunological mechanisms that are developed by placental cells in response to infection by both arboviruses. Here, we approach some of the current information available in the literature about the exacerbated presence of cells involved in the innate immune defense of the placenta during DENV and CHIKV infections.

Keywords: chikungunya; dengue; immune cells; innate immunity; interferon.

Figure 1

Schematic representation of the human maternal–fetal interface during DENV or CHIKV infection. DENV or CHIKV infection has immense potential to affect both maternal and fetal health. (A) During pregnancy, DENV infection can lead to thrombocytopenia, postpartum hemorrhage, miscarriage, and preeclampsia, in addition to representing an increased risk of neonatal death. (B) On the other hand, CHIKV infection can cause spontaneous abortion, postpartum hemorrhage, sepsis, intrauterine death, and preeclampsia and can also cause thrombocytopenia, fever, rash, irritability, and neurological disorders in the newborn. In the basal decidua are cells of the immune system: decidual natural killer (dNK) cells, dendritic cells, and maternal macrophages (dM). Chorionic villi contain trophoblast cells, Hofbauer cells (HBC), and fetal capillaries surrounded by a layer of cytotrophoblasts and multinucleated syncytiotrophoblast cells. The chorionic villus is floating in the intervillous space, bathed in maternal blood. So far, the mechanism involved in the vertical transmission of both viruses remains unclear. It is believed that vertical transmission can occur via the direct infection of trophoblasts (C) or syncytiotrophoblasts (D), as well as from breaches on the trophoblast layer (D) or via paracellular transport (C,D) from maternal blood to the fetal capillaries. The role of decidual immune system cells during DENV or CHIKV infection is not well established and nor is the IFN-I-mediated response, representing a gap in knowledge.