title: Human cytomegalovirus induces a distinct innate immune response in the maternal-fetal interface.
abstract: The initial interplay between human cytomegalovirus (HCMV) and innate tissue response in the human maternal-fetal interface, though crucial for determining the outcome of congenital HCMV infection, has remained unknown. We studied the innate response to HCMV within the milieu of the human decidua, the maternal aspect of the maternal-fetal interface, maintained ex vivo as an integral tissue. HCMV infection triggered a rapid and robust decidual-tissue innate immune response predominated by interferon (IFN)γ and IP-10 induction, dysregulating the decidual cytokine/chemokine environment in a distinctive fashion. The decidual-tissue response was already elicited during viral-tissue contact, and was not affected by neutralizing HCMV antibodies. Of note, IFNγ induction, reflecting immune-cell activation, was distinctive to the maternal decidua, and was not observed in concomitantly-infected placental (fetal) villi. Our studies in a clinically-relevant surrogate human model, provide a novel insight into the first-line decidual tissue response which could affect the outcome of congenital infection.
authors: Clinical Virology Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel; Department of Biochemistry and the Chanock Center for Virology, IMRIC, The Hebrew University Faculty of Medicine, Jerusalem, Israel.
authors: Yiska
authors: Y
authors: Weisblum
authors: Department of Biochemistry and the Chanock Center for Virology, IMRIC, The Hebrew University Faculty of Medicine, Jerusalem, Israel.
authors: Amos
authors: A
authors: Panet
authors: Department of Biochemistry and the Chanock Center for Virology, IMRIC, The Hebrew University Faculty of Medicine, Jerusalem, Israel.
authors: Zichria
authors: Z
authors: Zakay-Rones
authors: The Lautenberg Center for General and Tumor Immunology, IMRIC, The Hebrew University Faculty of Medicine, Jerusalem, Israel.
authors: Alon
authors: A
authors: Vitenshtein
authors: Department of Obstetrics and Gynecology, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors: Ronit
authors: R
authors: Haimov-Kochman
authors: Department of Obstetrics and Gynecology, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors: Debra
authors: D
authors: Goldman-Wohl
authors: Clinical Virology Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel; Department of Biochemistry and the Chanock Center for Virology, IMRIC, The Hebrew University Faculty of Medicine, Jerusalem, Israel.
authors: Esther
authors: E
authors: Oiknine-Djian
authors: The Lautenberg Center for General and Tumor Immunology, IMRIC, The Hebrew University Faculty of Medicine, Jerusalem, Israel.
authors: Rachel
authors: R
authors: Yamin
authors: Department of Pathology, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors: Karen
authors: K
authors: Meir
authors: Department of Obstetrics and Gynecology, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors: Hagai
authors: H
authors: Amsalem
authors: Department of Obstetrics and Gynecology, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors: Tal
authors: T
authors: Imbar
authors: The Lautenberg Center for General and Tumor Immunology, IMRIC, The Hebrew University Faculty of Medicine, Jerusalem, Israel.
authors: Ofer
authors: O
authors: Mandelboim
authors: Department of Obstetrics and Gynecology, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors: Simcha
authors: S
authors: Yagel
authors: Clinical Virology Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel. Electronic address: dana.wolf@ekmd.huji.ac.il.
authors: Dana G
authors: DG
authors: Wolf
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D003656:Decidua / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D005260:Female; D015870:Gene Expression; D006493:Heparin / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism; D010920:Placenta / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D011247:Pregnancy; D014771:Virion / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D016207:Cytokines; D018836:Inflammation Mediators; D006493:Heparin
keywords: Congenital viral infection; Decidua; Human cytomegalovirus; Innate immune response; Maternal–fetal interface; Placental infection