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

Yiska Weisblum; Amos Panet; Zichria Zakay-Rones; Alon Vitenshtein; Ronit Haimov-Kochman; Debra Goldman-Wohl; Esther Oiknine-Djian; Rachel Yamin; Karen Meir; Hagai Amsalem; Tal Imbar; Ofer Mandelboim; Simcha Yagel; Dana G. Wolf

doi:10.1016/j.virol.2015.06.023

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

Yiska Weisblum, Amos Panet, Zichria Zakay-Rones, Alon Vitenshtein, Ronit Haimov-Kochman, Debra Goldman-Wohl, Esther Oiknine-Djian, Rachel Yamin, Karen Meir, Hagai Amsalem, Tal Imbar, Ofer Mandelboim, Simcha Yagel, Dana G. Wolf^*

^*Corresponding author for this work

Department of Immunology and Cancer Research

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

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.

Original language	American English
Pages (from-to)	289-296
Number of pages	8
Journal	Virology
Volume	485
DOIs	https://doi.org/10.1016/j.virol.2015.06.023
State	Published - 1 Nov 2015

Bibliographical note

Funding Information:
This work was supported by grants from the Israel Science Foundation (grant number 275/13 ), the European Union Seventh Framework Programme 562 FP7/2012-2016 (grant agreement number 316655 ), and the Israeli Ministry of Health .

Publisher Copyright:
© 2015 Elsevier Inc.

Keywords

Congenital viral infection
Decidua
Human cytomegalovirus
Innate immune response
Maternal-fetal interface
Placental infection

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10.1016/j.virol.2015.06.023

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Weisblum, Y., Panet, A., Zakay-Rones, Z., Vitenshtein, A., Haimov-Kochman, R., Goldman-Wohl, D., Oiknine-Djian, E., Yamin, R., Meir, K., Amsalem, H., Imbar, T., Mandelboim, O., Yagel, S., & Wolf, D. G. (2015). Human cytomegalovirus induces a distinct innate immune response in the maternal-fetal interface. Virology, 485, 289-296. https://doi.org/10.1016/j.virol.2015.06.023

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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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AU - Vitenshtein, Alon

AU - Haimov-Kochman, Ronit

AU - Goldman-Wohl, Debra

AU - Oiknine-Djian, Esther

AU - Yamin, Rachel

AU - Meir, Karen

AU - Amsalem, Hagai

AU - Imbar, Tal

AU - Mandelboim, Ofer

AU - Yagel, Simcha

AU - Wolf, Dana G.

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N2 - 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.

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

Abstract

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Keywords

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