Cell Reports (Nov 2024)
SARS-CoV-2 infection elucidates features of pregnancy-specific immunity
- Dong Sun Oh,
- Eunha Kim,
- Rachelly Normand,
- Guangqing Lu,
- Lydia L. Shook,
- Amanda Lyall,
- Olyvia Jasset,
- Stepan Demidkin,
- Emily Gilbert,
- Joon Kim,
- Babatunde Akinwunmi,
- Jessica Tantivit,
- Alice Tirard,
- Benjamin Y. Arnold,
- Kamil Slowikowski,
- Marcia B. Goldberg,
- Michael R. Filbin,
- Nir Hacohen,
- Long H. Nguyen,
- Andrew T. Chan,
- Xu G. Yu,
- Jonathan Z. Li,
- Lael Yonker,
- Alessio Fasano,
- Roy H. Perlis,
- Ofer Pasternak,
- Kathryn J. Gray,
- Gloria B. Choi,
- David A. Drew,
- Pritha Sen,
- Alexandra-Chloé Villani,
- Andrea G. Edlow,
- Jun R. Huh
Affiliations
- Dong Sun Oh
- Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA
- Eunha Kim
- Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; BK21 Graduate Program, Department of Biomedical Sciences and Department of Neuroscience, Korea University College of Medicine, Seoul 02841, Republic of Korea
- Rachelly Normand
- Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA 02129, USA; Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA
- Guangqing Lu
- Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA
- Lydia L. Shook
- Department of Obstetrics, Gynecology and Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA 02114, USA
- Amanda Lyall
- Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
- Olyvia Jasset
- Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA 02114, USA
- Stepan Demidkin
- Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA 02114, USA
- Emily Gilbert
- Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA 02114, USA
- Joon Kim
- Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA 02114, USA
- Babatunde Akinwunmi
- Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA 02114, USA
- Jessica Tantivit
- Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA 02129, USA; Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Alice Tirard
- Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA 02129, USA; Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Benjamin Y. Arnold
- Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA 02129, USA; Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Kamil Slowikowski
- Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA 02129, USA; Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA
- Marcia B. Goldberg
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
- Michael R. Filbin
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
- Nir Hacohen
- Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
- Long H. Nguyen
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Harvard Chan Microbiome in Public Health Center, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
- Andrew T. Chan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Harvard Chan Microbiome in Public Health Center, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
- Xu G. Yu
- Infectious Disease Division, Brigham and Women’s Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA
- Jonathan Z. Li
- Division of Infectious Diseases, Brigham and Women’s Hospital, Boston, MA 02115, USA
- Lael Yonker
- Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02114, USA
- Alessio Fasano
- Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Boston, MA 02114, USA
- Roy H. Perlis
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
- Ofer Pasternak
- Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
- Kathryn J. Gray
- Department of Obstetrics & Gynecology, University of Washington, Seattle, WA 98195, USA
- Gloria B. Choi
- The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
- David A. Drew
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
- Pritha Sen
- Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA 02129, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA; Transplant, Oncology, and Immunocompromised Host Group, Division of Infectious Diseases, Brigham and Women’s Hospital, Boston, MA 02115, USA; Dana-Farber Cancer Institute, Boston, MA 02215, USA
- Alexandra-Chloé Villani
- Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA 02129, USA; Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA; Corresponding author
- Andrea G. Edlow
- Department of Obstetrics, Gynecology and Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Corresponding author
- Jun R. Huh
- Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Corresponding author
- Journal volume & issue
-
Vol. 43,
no. 11
p. 114933
Abstract
Summary: Pregnancy is a risk factor for increased severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory infections, but the mechanisms underlying this risk are poorly understood. To gain insight into the role of pregnancy in modulating immune responses at baseline and upon SARS-CoV-2 infection, we collected peripheral blood mononuclear cells and plasma from 226 women, including 152 pregnant individuals and 74 non-pregnant women. We find that SARS-CoV-2 infection is associated with altered T cell responses in pregnant women, including a clonal expansion of CD4-expressing CD8+ T cells, diminished interferon responses, and profound suppression of monocyte function. We also identify shifts in cytokine and chemokine levels in the sera of pregnant individuals, including a robust increase of interleukin-27, known to drive T cell exhaustion. Our findings reveal nuanced pregnancy-associated immune responses, which may contribute to the increased susceptibility of pregnant individuals to viral respiratory infection.