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

doi:10.1016/j.celrep.2024.113698

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

Biology

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

Abstract

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.

Original language	English
Article number	113698
Journal	Cell Reports
Volume	43
Issue number	2
DOIs	https://doi.org/10.1016/j.celrep.2024.113698
State	Published - 27 Feb 2024

Keywords

congenital CMV infection
CP: Immunology
decidual T cells
decidual tissues
ex vivo organ culture
human cytomegalovirus
maternal CMV infection
maternal-fetal interface
nonprimary CMV infection
placenta
tissue-resident T cells

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.celrep.2024.113698

Cite this

Alfi, O., Cohen, M., Bar-On, S., Hashimshony, T., Levitt, L., Raz, Y., Blecher, Y., Chaudhry, M. Z., Cicin-Sain, L., Ben-El, R., Oiknine-Djian, E., Lahav, T., Vorontsov, O., Cohen, A., Zakay-Rones, Z., Daniel, L., Berger, M., Mandel-Gutfreund, Y., Panet, A., & Wolf, D. G. (2024). Decidual-tissue-resident memory T cells protect against nonprimary human cytomegalovirus infection at the maternal-fetal interface. Cell Reports, 43(2), Article 113698. https://doi.org/10.1016/j.celrep.2024.113698

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title = "Decidual-tissue-resident memory T cells protect against nonprimary human cytomegalovirus infection at the maternal-fetal interface",

abstract = "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.",

keywords = "congenital CMV infection, CP: Immunology, decidual T cells, decidual tissues, ex vivo organ culture, human cytomegalovirus, maternal CMV infection, maternal-fetal interface, nonprimary CMV infection, placenta, tissue-resident T cells",

author = "Or Alfi and Mevaseret Cohen and Shikma Bar-On and Tamar Hashimshony and Lorinne Levitt and Yael Raz and Yair Blecher and Chaudhry, {M. Zeeshan} and Luka Cicin-Sain and Rina Ben-El and Esther Oiknine-Djian and Tamar Lahav and Olesya Vorontsov and Adiel Cohen and Zichria Zakay-Rones and Leonor Daniel and Michael Berger and Yael Mandel-Gutfreund and Amos Panet and Wolf, {Dana G.}",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s)",

year = "2024",

month = feb,

day = "27",

doi = "10.1016/j.celrep.2024.113698",

language = "אנגלית",

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Alfi, O, Cohen, M, Bar-On, S, Hashimshony, T, Levitt, L, Raz, Y, Blecher, Y, Chaudhry, MZ, Cicin-Sain, L, Ben-El, R, Oiknine-Djian, E, Lahav, T, Vorontsov, O, Cohen, A, Zakay-Rones, Z, Daniel, L, Berger, M, Mandel-Gutfreund, Y, Panet, A & Wolf, DG 2024, 'Decidual-tissue-resident memory T cells protect against nonprimary human cytomegalovirus infection at the maternal-fetal interface', Cell Reports, vol. 43, no. 2, 113698. https://doi.org/10.1016/j.celrep.2024.113698

TY - JOUR

T1 - Decidual-tissue-resident memory T cells protect against nonprimary human cytomegalovirus infection at the maternal-fetal interface

AU - Alfi, Or

AU - Cohen, Mevaseret

AU - Bar-On, Shikma

AU - Hashimshony, Tamar

AU - Levitt, Lorinne

AU - Raz, Yael

AU - Blecher, Yair

AU - Chaudhry, M. Zeeshan

AU - Cicin-Sain, Luka

AU - Ben-El, Rina

AU - Oiknine-Djian, Esther

AU - Lahav, Tamar

AU - Vorontsov, Olesya

AU - Cohen, Adiel

AU - Zakay-Rones, Zichria

AU - Daniel, Leonor

AU - Berger, Michael

AU - Mandel-Gutfreund, Yael

AU - Panet, Amos

AU - Wolf, Dana G.

PY - 2024/2/27

Y1 - 2024/2/27

N2 - 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.

AB - 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.

KW - congenital CMV infection

KW - CP: Immunology

KW - decidual T cells

KW - decidual tissues

KW - ex vivo organ culture

KW - human cytomegalovirus

KW - maternal CMV infection

KW - maternal-fetal interface

KW - nonprimary CMV infection

KW - placenta

KW - tissue-resident T cells

UR - http://www.scopus.com/inward/record.url?scp=85185191130&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2024.113698

DO - 10.1016/j.celrep.2024.113698

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C2 - 38265934

AN - SCOPUS:85185191130

SN - 2211-1247

VL - 43

JO - Cell Reports

JF - Cell Reports

IS - 2

M1 - 113698

ER -

Decidual-tissue-resident memory T cells protect against nonprimary human cytomegalovirus infection at the maternal-fetal interface

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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