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Human cytomegalovirus induces a distinct innate immune response in the maternal-fetal interface.

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      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.

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      Affiliations
      [1 ] 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.
      [2 ] Department of Biochemistry and the Chanock Center for Virology, IMRIC, The Hebrew University Faculty of Medicine, Jerusalem, Israel.
      [3 ] The Lautenberg Center for General and Tumor Immunology, IMRIC, The Hebrew University Faculty of Medicine, Jerusalem, Israel.
      [4 ] Department of Obstetrics and Gynecology, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
      [5 ] Department of Pathology, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
      [6 ] Clinical Virology Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel. Electronic address: dana.wolf@ekmd.huji.ac.il.
      Journal
      Virology
      Virology
      Elsevier BV
      1096-0341
      0042-6822
      Nov 2015
      : 485
      26318261
      S0042-6822(15)00301-3
      10.1016/j.virol.2015.06.023

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