Decidual-tissue-resident memory T cells protect against nonprimary human cytomegalovirus infection at the maternal-fetal interface
Or Alfi,
Mevaseret Cohen,
Shikma Bar-On,
Tamar Hashimshony,
Lorinne Levitt,
Yael Raz,
Yair Blecher,
M. Zeeshan Chaudhry,
Luka Cicin-Sain,
Rina Ben-El,
Esther Oiknine-Djian,
Tamar Lahav,
Olesya Vorontsov,
Adiel Cohen,
Zichria Zakay-Rones,
Leonor Daniel,
Michael Berger,
Yael Mandel-Gutfreund,
Amos Panet,
Dana G. Wolf
Affiliations
Or Alfi
Clinical Virology Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel; Department of Biochemistry, Institute for Medical Research Israel Canada, Faculty of Medicine, The Hebrew University, Jerusalem, Israel; Lautenberg Center for General and Tumor Immunology, Faculty of Medicine, The Hebrew University, Jerusalem, Israel
Mevaseret Cohen
Clinical Virology Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel; Department of Biochemistry, Institute for Medical Research Israel Canada, Faculty of Medicine, The Hebrew University, Jerusalem, Israel; Lautenberg Center for General and Tumor Immunology, Faculty of Medicine, The Hebrew University, Jerusalem, Israel
Shikma Bar-On
Lis Maternity Hospital, Tel Aviv Souraski Medical Center, Tel Aviv, Israel; Affiliated with the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Tamar Hashimshony
Faculty of Biology, Technion - Israel Institute of Technology, Haifa, Israel
Lorinne Levitt
Department of Obstetrics and Gynecology, Hadassah Hebrew University Medical Center and Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
Yael Raz
Lis Maternity Hospital, Tel Aviv Souraski Medical Center, Tel Aviv, Israel; Affiliated with the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Yair Blecher
Lis Maternity Hospital, Tel Aviv Souraski Medical Center, Tel Aviv, Israel; Affiliated with the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
M. Zeeshan Chaudhry
Department of Viral Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany; German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Braunschweig, Germany
Luka Cicin-Sain
Department of Viral Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany; German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Braunschweig, Germany; Centre for Individualised Infection Medicine (a joint venture of HZI and MHH), Hannover, Germany
Rina Ben-El
Faculty of Biology, Technion - Israel Institute of Technology, Haifa, Israel
Esther Oiknine-Djian
Clinical Virology Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel; Lautenberg Center for General and Tumor Immunology, Faculty of Medicine, The Hebrew University, Jerusalem, Israel
Tamar Lahav
Faculty of Biology, Technion - Israel Institute of Technology, Haifa, Israel
Olesya Vorontsov
Clinical Virology Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel; Department of Biochemistry, Institute for Medical Research Israel Canada, Faculty of Medicine, The Hebrew University, Jerusalem, Israel; Lautenberg Center for General and Tumor Immunology, Faculty of Medicine, The Hebrew University, Jerusalem, Israel
Adiel Cohen
Department of Obstetrics and Gynecology, Hadassah Hebrew University Medical Center and Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
Zichria Zakay-Rones
Department of Biochemistry, Institute for Medical Research Israel Canada, Faculty of Medicine, The Hebrew University, Jerusalem, Israel
Leonor Daniel
Lautenberg Center for General and Tumor Immunology, Faculty of Medicine, The Hebrew University, Jerusalem, Israel
Michael Berger
Lautenberg Center for General and Tumor Immunology, Faculty of Medicine, The Hebrew University, Jerusalem, Israel
Yael Mandel-Gutfreund
Faculty of Biology, Technion - Israel Institute of Technology, Haifa, Israel
Amos Panet
Department of Biochemistry, Institute for Medical Research Israel Canada, Faculty of Medicine, The Hebrew University, Jerusalem, Israel
Dana G. Wolf
Clinical Virology Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel; Lautenberg Center for General and Tumor Immunology, Faculty of Medicine, The Hebrew University, Jerusalem, Israel; Corresponding author
Summary: Congenital cytomegalovirus (cCMV) is the most common intrauterine infection, leading to infant neurodevelopmental disabilities. An improved knowledge of correlates of protection against cCMV is needed to guide prevention strategies. Here, we employ an ex vivo model of human CMV (HCMV) infection in decidual tissues of women with and without preconception immunity against CMV, recapitulating nonprimary vs. primary infection at the authentic maternofetal transmission site. We show that decidual tissues of women with preconception immunity against CMV exhibit intrinsic resistance to HCMV, mounting a rapid activation of tissue-resident memory CD8+ and CD4+ T cells upon HCMV reinfection. We further reveal the role of HCMV-specific decidual-tissue-resident CD8+ T cells in local protection against nonprimary HCMV infection. The findings could inform the development of a vaccine against cCMV and provide insights for further studies of the integrity of immune defense against HCMV and other pathogens at the human maternal-fetal interface.
