Placental myeloid cells protect against Zika virus vertical transmission in a murine model

Abstract The ability of Zika virus (ZIKV) to cross the placenta and infect the fetus is a key mechanism by which ZIKV causes microcephaly. How the virus crosses the placenta and the role of the immune response in this process remain unclear. In the current study, we examined how ZIKV infection affected the immune cells within the placenta and developing fetus and whether these cells influenced virus vertical transmission (VTx). We found myeloid cells were elevated in the placenta of pregnant mice infected with ZIKV, primarily at the end of pregnancy, as well as in the fetus several days before birth. These cells, which included maternal monocytes/macrophages, neutrophils and fetal myeloid cells contained high levels of viral RNA suggesting they may be infected and contributing to viral replication and VTx. However, depletion of monocyte/macrophage myeloid cells from the dam during ZIKV infection resulted in increased ZIKV infection in the fetus. Myeloid cells were not depleted in the fetus in this experiment, so the increased virus infection was not the result of an impaired fetal myeloid response. Collectively, these data suggest that monocyte/macrophage myeloid cells in the placenta play a significant role in inhibiting ZIKV VTx to the fetus, possibly through phagocytosis of virus or virus infected cells.