TY - JOUR
T1 - Immune Profile of the Normal Maternal-Fetal Interface in Rhesus Macaques and Its Alteration Following Zika Virus Infection
AU - Moström, Matilda J.
AU - Scheef, Elizabeth A.
AU - Sprehe, Lesli M.
AU - Szeltner, Dawn
AU - Tran, Dollnovan
AU - Hennebold, Jon D.
AU - Roberts, Victoria H.J.
AU - Maness, Nicholas J.
AU - Fahlberg, Marissa
AU - Kaur, Amitinder
N1 - Funding Information:
Funding was provided by NIH by 1P01AI129859, TNPRC Base Grant OD011104, and ONPRC Base Grant OD011092. Additional funding for the ZIKV-infected study group was provided by the Bill and Melinda Gates Foundation (OPP1152818). Animal samples were available through the ONPRC Pathology tissue distribution program, which is supported by ONPRC NIH Base Grant OD011092.
Funding Information:
The authors would like to acknowledge the TNPRC Flow Core, Megan Varnado, Natalie Guy, and Kaitlin Didier for the flow cytometry support. Both the TNPRC and ONPRC veterinary medicine teams provided animal care and procured samples. Teresa Beechwood for shipping samples from OHSU to Tulane. In addition, Blake Schouest is acknowledged for assisting with literature references. The authors would like to thank the NIH Tetramer Core facility for provision of the CD1dTM conjugated to BV421.
Publisher Copyright:
© Copyright © 2021 Moström, Scheef, Sprehe, Szeltner, Tran, Hennebold, Roberts, Maness, Fahlberg and Kaur.
PY - 2021/7/29
Y1 - 2021/7/29
N2 - The maternal decidua is an immunologically complex environment that balances maintenance of immune tolerance to fetal paternal antigens with protection of the fetus against vertical transmission of maternal pathogens. To better understand host immune determinants of congenital infection at the maternal-fetal tissue interface, we performed a comparative analysis of innate and adaptive immune cell subsets in the peripheral blood and decidua of healthy rhesus macaque pregnancies across all trimesters of gestation and determined changes after Zika virus (ZIKV) infection. Using one 28-color and one 18-color polychromatic flow cytometry panel we simultaneously analyzed the frequency, phenotype, activation status and trafficking properties of αβ T, γδ T, iNKT, regulatory T (Treg), NK cells, B lymphocytes, monocytes, macrophages, and dendritic cells (DC). Decidual leukocytes showed a striking enrichment of activated effector memory and tissue-resident memory CD4+ and CD8+ T lymphocytes, CD4+ Tregs, CD56+ NK cells, CD14+CD16+ monocytes, CD206+ tissue-resident macrophages, and a paucity of B lymphocytes when compared to peripheral blood. t-distributed stochastic neighbor embedding (tSNE) revealed unique populations of decidual NK, T, DC and monocyte/macrophage subsets. Principal component analysis showed distinct spatial localization of decidual and circulating leukocytes contributed by NK and CD8+ T lymphocytes, and separation of decidua based on gestational age contributed by memory CD4+ and CD8+ T lymphocytes. Decidua from 10 ZIKV-infected dams obtained 16-56 days post infection at third (n=9) or second (n=1) trimester showed a significant reduction in frequency of activated, CXCR3+, and/or Granzyme B+ memory CD4+ and CD8+ T lymphocytes and γδ T compared to normal decidua. These data suggest that ZIKV induces local immunosuppression with reduced immune recruitment and impaired cytotoxicity. Our study adds to the immune characterization of the maternal-fetal interface in a translational nonhuman primate model of congenital infection and provides novel insight in to putative mechanisms of vertical transmission.
AB - The maternal decidua is an immunologically complex environment that balances maintenance of immune tolerance to fetal paternal antigens with protection of the fetus against vertical transmission of maternal pathogens. To better understand host immune determinants of congenital infection at the maternal-fetal tissue interface, we performed a comparative analysis of innate and adaptive immune cell subsets in the peripheral blood and decidua of healthy rhesus macaque pregnancies across all trimesters of gestation and determined changes after Zika virus (ZIKV) infection. Using one 28-color and one 18-color polychromatic flow cytometry panel we simultaneously analyzed the frequency, phenotype, activation status and trafficking properties of αβ T, γδ T, iNKT, regulatory T (Treg), NK cells, B lymphocytes, monocytes, macrophages, and dendritic cells (DC). Decidual leukocytes showed a striking enrichment of activated effector memory and tissue-resident memory CD4+ and CD8+ T lymphocytes, CD4+ Tregs, CD56+ NK cells, CD14+CD16+ monocytes, CD206+ tissue-resident macrophages, and a paucity of B lymphocytes when compared to peripheral blood. t-distributed stochastic neighbor embedding (tSNE) revealed unique populations of decidual NK, T, DC and monocyte/macrophage subsets. Principal component analysis showed distinct spatial localization of decidual and circulating leukocytes contributed by NK and CD8+ T lymphocytes, and separation of decidua based on gestational age contributed by memory CD4+ and CD8+ T lymphocytes. Decidua from 10 ZIKV-infected dams obtained 16-56 days post infection at third (n=9) or second (n=1) trimester showed a significant reduction in frequency of activated, CXCR3+, and/or Granzyme B+ memory CD4+ and CD8+ T lymphocytes and γδ T compared to normal decidua. These data suggest that ZIKV induces local immunosuppression with reduced immune recruitment and impaired cytotoxicity. Our study adds to the immune characterization of the maternal-fetal interface in a translational nonhuman primate model of congenital infection and provides novel insight in to putative mechanisms of vertical transmission.
KW - Treg
KW - Zika
KW - congenital viral infection
KW - dNK
KW - decidua
KW - decidual T cells
KW - fetal-maternal immunity
KW - gammadelta T cells
UR - http://www.scopus.com/inward/record.url?scp=85112431444&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85112431444&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2021.719810
DO - 10.3389/fimmu.2021.719810
M3 - Article
C2 - 34394129
AN - SCOPUS:85112431444
SN - 1664-3224
VL - 12
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 719810
ER -