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
Affiliations
Suhas Sureshchandra
Department of Molecular Biology and Biochemistry, School of Biological Sciences, University of California, Irvine, CA 92697, USA; Institute for Immunology, University of California, Irvine, CA 92697, USA
Michael Z. Zulu
Department of Molecular Biology and Biochemistry, School of Biological Sciences, University of California, Irvine, CA 92697, USA; Institute for Immunology, University of California, Irvine, CA 92697, USA
Brianna M. Doratt
Department of Molecular Biology and Biochemistry, School of Biological Sciences, University of California, Irvine, CA 92697, USA; Institute for Immunology, University of California, Irvine, CA 92697, USA; Department of Microbiology, Immunology, and Molecular Genetics, College of Medicine, University of Kentucky, Lexington, KY 40536, USA
Allen Jankeel
Department of Molecular Biology and Biochemistry, School of Biological Sciences, University of California, Irvine, CA 92697, USA
Delia Tifrea
Department of Pathology and Laboratory Medicine, School of Medicine, University of California, Irvine, CA 92697, USA
Robert Edwards
Department of Pathology and Laboratory Medicine, School of Medicine, University of California, Irvine, CA 92697, USA
Monica Rincon
Maternal-Fetal Medicine, Oregon Health and Sciences University, Portland, OR 97239, USA
Nicole E. Marshall
Maternal-Fetal Medicine, Oregon Health and Sciences University, Portland, OR 97239, USA
Ilhem Messaoudi
Department of Molecular Biology and Biochemistry, School of Biological Sciences, University of California, Irvine, CA 92697, USA; Institute for Immunology, University of California, Irvine, CA 92697, USA; Department of Microbiology, Immunology, and Molecular Genetics, College of Medicine, University of Kentucky, Lexington, KY 40536, USA; Corresponding author
Summary: 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.
