IFITM1 inhibits trophoblast invasion and is induced in placentas associated with IFN-mediated pregnancy diseases
Séverine A. Degrelle,
Julian Buchrieser,
Anne Dupressoir,
Françoise Porrot,
Laurence Loeuillet,
Olivier Schwartz,
Thierry Fournier
Affiliations
Séverine A. Degrelle
Université Paris Cité, INSERM, UMR-S1139, Pathophysiology & Pharmacotoxicology of the Human Placenta, Pre- & Post-natal Microbiota (3PHM), 75006 Paris, France; Inovarion, 75005 Paris, France; Corresponding author
Julian Buchrieser
Virus and Immunity Unit, Institut Pasteur, 75015 Paris, France; CNRS-UMR3569, 75015 Paris, France
Anne Dupressoir
Unité Physiologie et Pathologie Moléculaires des Rétrovirus Endogènes et Infectieux, Hôpital Gustave Roussy, 94805 Villejuif, France; UMR 9196, Université Paris-Sud, 91405 Orsay, France
Françoise Porrot
Unité Physiologie et Pathologie Moléculaires des Rétrovirus Endogènes et Infectieux, Hôpital Gustave Roussy, 94805 Villejuif, France; UMR 9196, Université Paris-Sud, 91405 Orsay, France
Laurence Loeuillet
Service d'Histologie-Embryologie-Cytogénétique, Hôpital Necker-Enfants Malades, AP-HP, 75015 Paris, France
Olivier Schwartz
Virus and Immunity Unit, Institut Pasteur, 75015 Paris, France; CNRS-UMR3569, 75015 Paris, France; Vaccine Research Institute, 94010 Créteil, France
Thierry Fournier
Université Paris Cité, INSERM, UMR-S1139, Pathophysiology & Pharmacotoxicology of the Human Placenta, Pre- & Post-natal Microbiota (3PHM), 75006 Paris, France
Summary: Interferon-induced transmembrane proteins (IFITMs) are restriction factors that block many viruses from entering cells. High levels of type I interferon (IFN) are associated with adverse pregnancy outcomes, and IFITMs have been shown to impair the formation of syncytiotrophoblast. Here, we examine whether IFITMs affect another critical step of placental development, extravillous cytotrophoblast (EVCT) invasion. We conducted experiments using in vitro/ex vivo models of EVCT, mice treated in vivo with the IFN-inducer poly (I:C), and human pathological placental sections. Cells treated with IFN-β demonstrated upregulation of IFITMs and reduced invasive abilities. Transduction experiments confirmed that IFITM1 contributed to the decreased cell invasion. Similarly, migration of trophoblast giant cells, the mouse equivalent of human EVCTs, was significantly reduced in poly (I:C)-treated mice. Finally, analysis of CMV- and bacterial-infected human placentas revealed upregulated IFITM1 expression. These data demonstrate that high levels of IFITM1 impair trophoblast invasion and could explain the placental dysfunctions associated with IFN-mediated disorders.
