Maternal SARS-CoV-2 infection in pregnancy disrupts gene expression in Hofbauer cells with limited impact on cytotrophoblasts.

Autor: Enninga EAL; Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota, United States of America.; Department of Immunology, Mayo Clinic, Rochester, Minnesota, United States of America., Quach HQ; Mayo Clinic Vaccine Research Group, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, United States of America., Jang JS; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America., de Araujo Correia MCM; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, United States of America., Fedyshyn Y; Children Research Center, Division of Pediatric Infectious Diseases, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, United States of America., Fedyshyn B; Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota, United States of America., Lemens M; Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota, United States of America., Littlefield D; Children Research Center, Division of Pediatric Infectious Diseases, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, United States of America., Behl S; Children Research Center, Division of Pediatric Infectious Diseases, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, United States of America., Sintim-Aboagye E; Children Research Center, Division of Pediatric Infectious Diseases, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, United States of America., Mejia Plazas MC; Children Research Center, Division of Pediatric Infectious Diseases, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, United States of America., Cardenas MC; Children Research Center, Division of Pediatric Infectious Diseases, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, United States of America., Chakraborty S; Children Research Center, Division of Pediatric Infectious Diseases, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, United States of America., Yamaoka S; Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, United States of America., Ebihara H; Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, United States of America., Pandey A; Department of Laboratory Medicine and Pathology, Division of Clinical Biochemistry and Immunology, Mayo Clinic, Rochester, Minnesota, United States of America.; Center for Molecular Medicine, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.; Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, United States of America., Li H; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, United States of America., Badley AD; Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota, United States of America., Johnson EL; Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, Georgia, United States of America., Sun J; Thoracic Diseases Research Unit, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Department of Immunology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, United States of America.; Carter Immunology Center University of Virginia School of Medicine, Charlottesville, Virginia, United States of America., Norgan AP; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America., Theiler RN; Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota, United States of America., Chakraborty R; Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota, United States of America.; Department of Immunology, Mayo Clinic, Rochester, Minnesota, United States of America.; Children Research Center, Division of Pediatric Infectious Diseases, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2024 Feb 07; Vol. 20 (2), pp. e1011990. Date of Electronic Publication: 2024 Feb 07 (Print Publication: 2024).
DOI: 10.1371/journal.ppat.1011990
Abstrakt: Background: Hofbauer cells (HBCs) and cytotrophoblasts (CTBs) are major cell populations in placenta. The indirect impact of maternal SARS-CoV-2 disease on these cells that are not directly infected has not been extensively studied. Herein, we profiled gene expression in HBCs and CTBs isolated from placentae of recovered pregnant subjects infected with SARS-CoV-2 during all trimesters of pregnancy, placentae from subjects with active infection, SARS-CoV-2 vaccinated subjects, and those who were unexposed to the virus.
Methods: Placentae were collected within 4 h post-delivery and membrane-free tissues were enzymatically digested for the isolation of HBCs and CTBs. RNA extracted from HBCs and CTBs were sequenced using 150bp paired-end reads. Differentially expressed genes (DEGs) were identified by DESeq2 package in R and enriched in GO Biological Processes, KEGG Pathway, Reactome Gene Sets, Hallmark Gene Sets, and Canonical Pathways. Protein-protein interactions among the DEGs were modelled using STRING and BioGrid.
Results: Pregnant subjects (n = 30) were recruited and categorized into six groups: infected with SARS-CoV-2 in i) the first (1T, n = 4), ii) second (2T, n = 5), iii) third (3T, n = 5) trimester, iv) tested positive at delivery (Delivery, n = 5), v) never infected (Control, n = 6), and vi) fully mRNA-vaccinated by delivery (Vaccinated, n = 5). Compared to the Control group, gene expression analysis showed that HBCs from infected subjects had significantly altered gene expression profiles, with the 2T group having the highest number of DEGs (1,696), followed by 3T and 1T groups (1,656 and 958 DEGs, respectively). These DEGs were enriched for pathways involved in immune regulation for host defense, including production of cytokines, chemokines, antimicrobial proteins, ribosomal assembly, neutrophil degranulation inflammation, morphogenesis, and cell migration/adhesion. Protein-protein interaction analysis mapped these DEGs with oxidative phosphorylation, translation, extracellular matrix organization, and type I interferon signaling. Only 95, 23, and 8 DEGs were identified in CTBs of 1T, 2T, and 3T groups, respectively. Similarly, 11 and 3 DEGs were identified in CTBs and HBCs of vaccinated subjects, respectively. Reassuringly, mRNA vaccination did not induce an inflammatory response in placental cells.
Conclusions: Our studies demonstrate a significant impact of indirect SARS-CoV-2 infection on gene expression of inner mesenchymal HBCs, with limited effect on lining CTB cells isolated from pregnant subjects infected and recovered from SARS-CoV-2. The pathways associated with these DEGs identify potential targets for therapeutic intervention.
Competing Interests: Dr. Theiler has research support and a know-how agreement with HeraMed and is a member of the Delfina Medical Advisory Board. Dr. Badley is a paid consultant for Abbvie, Gilead, Freedom Tunnel, Pinetree therapeutics Primmune, Immunome, MarPam, Rion, Symbiosis, NexImmune and Flambeau Diagnostics, is a paid member of the DSMB for Corvus Pharmaceuticals, Equilium, CSL Behring, and Excision Biotherapeutics, has received fees for speaking for Reach MD, Peer Voice, and Medscape, owns equity for scientific advisory work in Tier 1 Bio, Zentalis, Rion, and Nference, and is founder and President of Splissen therapeutics, and Member of the Board of Attivare. These activities have been reviewed by the Mayo Clinic Conflict of Interest Review Board and are conducted in compliance with Mayo Clinic Conflict of Interest policies. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and was conducted in compliance with Mayo Clinic Conflict of Interest policies. Other authors have declared that no conflict of interest exists.
(Copyright: © 2024 Enninga et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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