Single-cell RNA sequencing reveals immunological rewiring at the maternal-fetal interface following asymptomatic/mild SARS-CoV-2 infection

Suhas Sureshchandra; Michael Z. Zulu; Brianna M. Doratt; Allen Jankeel; Delia Tifrea; Robert Edwards; Monica Rincon; Nicole E. Marshall; Ilhem Messaoudi

doi:10.1016/j.celrep.2022.110938

Single-cell RNA sequencing reveals immunological rewiring at the maternal-fetal interface following asymptomatic/mild SARS-CoV-2 infection

Suhas Sureshchandra
, Michael Z. Zulu
, Brianna M. Doratt
, Allen Jankeel
, Delia Tifrea
, Robert Edwards
, Monica Rincon
, Nicole E. Marshall
, Ilhem Messaoudi

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

30 Scopus citations

Abstract

While severe coronavirus 2019 (COVID-19) is associated with immune activation at the maternal-fetal interface, responses to asymptomatic/mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy remain unknown. Here, we assess immunological adaptations in blood and term decidua in response to asymptomatic/mild disease in pregnant women. We report attenuated antigen presentation and type I interferon (IFN) signaling pathways, loss of tissue-resident decidual macrophages, and upregulated cytokine/chemokine signaling in monocyte-derived decidual macrophages. Furthermore, we describe increased frequencies of activated tissue-resident T cells and decreased abundance of regulatory T cells with infection while frequencies of cytotoxic CD4/CD8 T cells are increased in the blood. In contrast to decidual macrophages, type I IFN signaling is higher in decidual T cells. Finally, infection leads to a narrowing of T cell receptor diversity in both blood and decidua. Collectively, these observations indicate that asymptomatic/mild COVID-19 during pregnancy results in remodeling of the immunological landscape of the maternal-fetal interface, with a potential for long-term adverse outcomes for the offspring.

Original language	English
Article number	110938
Journal	Cell Reports
Volume	39
Issue number	11
DOIs	https://doi.org/10.1016/j.celrep.2022.110938
State	Published - Jun 14 2022

Bibliographical note

Publisher Copyright:
© 2022 The Author(s)

Funding

We are grateful to all participants in this study. We thank the MFM Research Unit at OHSU for sample collection. We thank Dr. Jennifer Atwood for assistance with sorting at the Flow Cytometry Core at the Institute for Immunology, UCI. We thank the UCI Genomics and High-Throughput Facility for assistance with 10X library sequencing. Aspects of experimental design figures were generated using graphics from Biorender.com. This study was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health through grants UL1TR001414, 1R01AI142841, and 1R01AI145910. The authors also wish to acknowledge the support of the Chao Family Comprehensive Cancer Center Experimental Tissue Shared Resource, supported by the National Cancer Institute of the NIH under award number P30CA062203. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Conceptualization, S.S. N.E.M. and I.M.; methodology, S.S. N.E.M. and I.M.; investigation, S.S. M.Z.Z. B.M.D. and A.J.; writing, S.S. and I.M.; funding acquisition, N.E.M. and I.M.; resources, M.R. D.T. and R.E. All authors have read and approved the final draft of the manuscript. The authors declare no competing interests. We are grateful to all participants in this study. We thank the MFM Research Unit at OHSU for sample collection. We thank Dr. Jennifer Atwood for assistance with sorting at the Flow Cytometry Core at the Institute for Immunology, UCI. We thank the UCI Genomics and High-Throughput Facility for assistance with 10X library sequencing. Aspects of experimental design figures were generated using graphics from Biorender.com . This study was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health through grants UL1TR001414 , 1R01AI142841 , and 1R01AI145910 . The authors also wish to acknowledge the support of the Chao Family Comprehensive Cancer Center Experimental Tissue Shared Resource, supported by the National Cancer Institute of the NIH under award number P30CA062203 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Funders	Funder number
Oregon Health and Science University
National Institutes of Health (NIH)
National Center for Research Resources
National Childhood Cancer Registry – National Cancer Institute	P30CA062203
National Center for Advancing Translational Sciences (NCATS)	UL1TR001414
National Institute of Allergy and Infectious Diseases	R01AI142841, R01AI145910
UK Industrial Decarbonization Research and Innovation Centre	103464

Keywords

COVID-19
CP: Immunology
CP: Microbiology
SARS-CoV-2
T cells
TCR
decidua
macrophages
placenta
pregnancy

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2022.110938

Cite this

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title = "Single-cell RNA sequencing reveals immunological rewiring at the maternal-fetal interface following asymptomatic/mild SARS-CoV-2 infection",

abstract = "While severe coronavirus 2019 (COVID-19) is associated with immune activation at the maternal-fetal interface, responses to asymptomatic/mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy remain unknown. Here, we assess immunological adaptations in blood and term decidua in response to asymptomatic/mild disease in pregnant women. We report attenuated antigen presentation and type I interferon (IFN) signaling pathways, loss of tissue-resident decidual macrophages, and upregulated cytokine/chemokine signaling in monocyte-derived decidual macrophages. Furthermore, we describe increased frequencies of activated tissue-resident T cells and decreased abundance of regulatory T cells with infection while frequencies of cytotoxic CD4/CD8 T cells are increased in the blood. In contrast to decidual macrophages, type I IFN signaling is higher in decidual T cells. Finally, infection leads to a narrowing of T cell receptor diversity in both blood and decidua. Collectively, these observations indicate that asymptomatic/mild COVID-19 during pregnancy results in remodeling of the immunological landscape of the maternal-fetal interface, with a potential for long-term adverse outcomes for the offspring.",

keywords = "COVID-19, CP: Immunology, CP: Microbiology, SARS-CoV-2, T cells, TCR, decidua, macrophages, placenta, pregnancy",

author = "Suhas Sureshchandra and Zulu, \{Michael Z.\} and Doratt, \{Brianna M.\} and Allen Jankeel and Delia Tifrea and Robert Edwards and Monica Rincon and Marshall, \{Nicole E.\} and Ilhem Messaoudi",

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doi = "10.1016/j.celrep.2022.110938",

language = "English",

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AU - Sureshchandra, Suhas

AU - Zulu, Michael Z.

AU - Doratt, Brianna M.

AU - Jankeel, Allen

AU - Tifrea, Delia

AU - Edwards, Robert

AU - Rincon, Monica

AU - Marshall, Nicole E.

AU - Messaoudi, Ilhem

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N2 - While severe coronavirus 2019 (COVID-19) is associated with immune activation at the maternal-fetal interface, responses to asymptomatic/mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy remain unknown. Here, we assess immunological adaptations in blood and term decidua in response to asymptomatic/mild disease in pregnant women. We report attenuated antigen presentation and type I interferon (IFN) signaling pathways, loss of tissue-resident decidual macrophages, and upregulated cytokine/chemokine signaling in monocyte-derived decidual macrophages. Furthermore, we describe increased frequencies of activated tissue-resident T cells and decreased abundance of regulatory T cells with infection while frequencies of cytotoxic CD4/CD8 T cells are increased in the blood. In contrast to decidual macrophages, type I IFN signaling is higher in decidual T cells. Finally, infection leads to a narrowing of T cell receptor diversity in both blood and decidua. Collectively, these observations indicate that asymptomatic/mild COVID-19 during pregnancy results in remodeling of the immunological landscape of the maternal-fetal interface, with a potential for long-term adverse outcomes for the offspring.

AB - While severe coronavirus 2019 (COVID-19) is associated with immune activation at the maternal-fetal interface, responses to asymptomatic/mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy remain unknown. Here, we assess immunological adaptations in blood and term decidua in response to asymptomatic/mild disease in pregnant women. We report attenuated antigen presentation and type I interferon (IFN) signaling pathways, loss of tissue-resident decidual macrophages, and upregulated cytokine/chemokine signaling in monocyte-derived decidual macrophages. Furthermore, we describe increased frequencies of activated tissue-resident T cells and decreased abundance of regulatory T cells with infection while frequencies of cytotoxic CD4/CD8 T cells are increased in the blood. In contrast to decidual macrophages, type I IFN signaling is higher in decidual T cells. Finally, infection leads to a narrowing of T cell receptor diversity in both blood and decidua. Collectively, these observations indicate that asymptomatic/mild COVID-19 during pregnancy results in remodeling of the immunological landscape of the maternal-fetal interface, with a potential for long-term adverse outcomes for the offspring.

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Single-cell RNA sequencing reveals immunological rewiring at the maternal-fetal interface following asymptomatic/mild SARS-CoV-2 infection

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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