Wavering Between Passive and Aggressive

Abstract

Immune cells at the maternal-fetal interface lack punch— they are weak and disarmed, shielding the fetus from attack by the mother. But how do such cells also manage to attack infectious agents like viruses? A new study of human tissue suggests that immune cells at the maternal-fetal interface can shuttle between a non-activated and an activated state in response to viral infection [1]. In early pregnancy, the maternal-fetal interface is populated by decidual NK (dNK) cells. These NK cells are in a tolerogenic, low-activity state, which is thought to be induced in part via HLA-G, a molecule expressed almost exclusively in fetal extravillous trophoblasts (EVTs)—cells that invade maternal decidual tissue during pregnancy. Tamara Tilburgs and J. Henry Evans et al. examined cocultures of primary EVT and dNK with high-resolution confocal microscopy. They report that filopodia from EVT make contacts with dNK cells (Fig. 1). They also provide evidence that the EVT transfer HLA-G to dNK cells via a form of direct transfer, trogocytosis (from the ancient Greek trogo, meaning ‘gnaw’). The researchers then activated the dNK cells in culture with IL-15, which is known to ramp up dNK cell-killing activity. They found that culture with IL-15 resulted in the disappearance of HLA-G from dNK cells. The researchers also exposed dNK cells to cells infected with HCMV (human cytomegalo virus), a common infection during pregnancy—and found an increase in cytotoxicity, an effect amplified by IL-15. Finally, they showed that dNK cells exposed to IL-15 could re-acquire HLA-G upon culture with EVT. The findings suggest that dNK cells can switch between tolerance and antiviral immunity through the acquisition and disappearance of HLA-G.