Ronit Haimov-Kochman1, Yiska Weisblum2,3, Amos Panet2, Zichria Zakay-Rones3, Caryn Greenfield1,Tal Imbar1, , Debra Goldman-Wohl1 and Dana G Wolf2 and Simcha Yagel1
1Obstetrics and Gynecology;2Clinical Virology Unit, Center, Jerusalem, Israel and 3Biochemistry and the Chanock Center for Virology,Hadassah Hebrew University Medical Center, Jerusalem, Israel.
Introduction: Human cytomegalovirus (HCMV) is a leading cause of congenital infection, associated with birth defects and placental insufficiency. The initial stages of infection occur in the maternal decidua – representing the maternal aspect of the chimeric human placenta.
Methods: We employed our recently established ex vivo model of HCMV infection in human decidual organ cultures, to characterize the tissue innate immune response to HCMV within the natural multi-cell-type milieu of the maternal-fetal interface.
Results: HCMV infection triggered a rapid immune activation in the decidua, significantly affecting decidual cytokine -chemokine expression pattern, with predominant induction of interferon (IFN)-γ and IP-10. Decidual tissue innate response was induced early upon virus-tissue contact by a conserved structural virion component, and was not affected by neutralizing HCMV antibodies. Of note, IFN-γ induction was distinctive to the decidual tissue, and was not observed in concomitantly- infected placental villi. Importantly, functional analysis of conditioned media recovered from infected tissues revealed the direct effect of the viral-induced decidual environment on antiviral protection along with leukocyte attraction and induction of apoptosis.
Conclusions: These studies, in a clinically-relevant surrogate human model, provide a novel insight into the first-line tissue response, mediating both protection and damage in the maternal-fetal interface, which could determine the outcome of infection.