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

doi:10.1016/j.isci.2023.107147

IFITM1 inhibits trophoblast invasion and is induced in placentas associated with IFN-mediated pregnancy diseases

iScience. 2023 Jun 15;26(7):107147. doi: 10.1016/j.isci.2023.107147. eCollection 2023 Jul 21.

Authors

Séverine A Degrelle^{1

2}, Julian Buchrieser^{3

4}, Anne Dupressoir^{5

6}, Françoise Porrot^{5

6}, Laurence Loeuillet⁷, Olivier Schwartz^{3

4

8}, Thierry Fournier¹

Affiliations

¹ Université Paris Cité, INSERM, UMR-S1139, Pathophysiology & Pharmacotoxicology of the Human Placenta, Pre- & Post-natal Microbiota (3PHM), 75006 Paris, France.
² Inovarion, 75005 Paris, France.
³ Virus and Immunity Unit, Institut Pasteur, 75015 Paris, France.
⁴ CNRS-UMR3569, 75015 Paris, France.
⁵ Unité Physiologie et Pathologie Moléculaires des Rétrovirus Endogènes et Infectieux, Hôpital Gustave Roussy, 94805 Villejuif, France.
⁶ UMR 9196, Université Paris-Sud, 91405 Orsay, France.
⁷ Service d'Histologie-Embryologie-Cytogénétique, Hôpital Necker-Enfants Malades, AP-HP, 75015 Paris, France.
⁸ Vaccine Research Institute, 94010 Créteil, France.

Abstract

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.

Keywords: Biological sciences; Cell biology; Virology.