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.
N1 - Publisher Copyright:
© 2024 The Author(s)
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 - CP: Immunology
KW - congenital CMV infection
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 -