Maternal obesity blunts antimicrobial responses in fetal monocytes

  1. Suhas Sureshchandra
  2. Brianna M Doratt
  3. Norma Mendza
  4. Oleg Varlamov
  5. Monica Rincon
  6. Nicole E Marshall
  7. Ilhem Messaoudi  Is a corresponding author
  1. University of California, Irvine, United States
  2. University of Kentucky, United States
  3. Oregon Health & Science University, United States

Abstract

Maternal pre-pregnancy (pregravid) obesity is associated with adverse outcomes for both mother and offspring. Amongst the complications for the offspring is increased susceptibility and severity of neonatal infections necessitating admission to the intensive care unit, notably bacterial sepsis and enterocolitis. Previous studies have reported aberrant responses to LPS and polyclonal stimulation by umbilical cord blood monocytes that were mediated by alterations in the epigenome. In this study, we show that pregravid obesity dysregulates umbilical cord blood monocyte responses to bacterial and viral pathogens. Specifically, interferon-stimulated gene expression and inflammatory responses to respiratory syncytial virus (RSV) and E. coli respectively were significantly dampened. Although upstream signaling events were comparable, translocation of the key transcription factor NF-kB and chromatin accessibility at pro-inflammatory gene promoters following TLR stimulation was significantly attenuated. Using a rhesus macaque model of western style diet-induced obesity, we further demonstrate that this defect is detected in fetal peripheral monocytes and tissue-resident macrophages during gestation. Collectively, these data indicate that maternal obesity alters metabolic, signaling, and epigenetic profiles of fetal monocytes leading to a state of immune paralysis during late gestation and at birth.

Data availability

The datasets supporting the conclusions of this article are available on NCBI's Sequence Read Archive PRJNA847067 and PRJNA914662.

The following data sets were generated

Article and author information

Author details

  1. Suhas Sureshchandra

    Institute for Immunology, University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Brianna M Doratt

    Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexingtion, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8107-724X
  3. Norma Mendza

    Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Oleg Varlamov

    Division of Cardiometabolic Health, Oregon Health & Science University, Beaverton, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Monica Rincon

    Maternal-Fetal Medicine, Oregon Health & Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5574-585X
  6. Nicole E Marshall

    Maternal-Fetal Medicine, Oregon Health & Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Ilhem Messaoudi

    Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexingtion, United States
    For correspondence
    ilhem.messaoudi@uky.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3203-2405

Funding

National Institute of Allergy and Infectious Diseases (R03AI112808)

  • Ilhem Messaoudi

National Institute of Allergy and Infectious Diseases (1R01AI142841)

  • Ilhem Messaoudi

National Institute of Allergy and Infectious Diseases (1R01AI145910)

  • Ilhem Messaoudi

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: This study was approved by the Institutional Ethics Review Board of Oregon Health and Science University (STUDY00020735 "Perinatant Early Determinants of Immune Development") and the University of California, Irvine (protocol number 2017-3397 "Impact of maternal pre-pregnancy obesity on the offspring immune system"). Written consent was obtained from all subjects.

Reviewing Editor

  1. Jalees Rehman, University of Illinois at Chicago, United States

Publication history

  1. Received: June 22, 2022
  2. Accepted: January 15, 2023
  3. Accepted Manuscript published: January 16, 2023 (version 1)

Copyright

© 2023, Sureshchandra et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Suhas Sureshchandra
  2. Brianna M Doratt
  3. Norma Mendza
  4. Oleg Varlamov
  5. Monica Rincon
  6. Nicole E Marshall
  7. Ilhem Messaoudi
(2023)
Maternal obesity blunts antimicrobial responses in fetal monocytes
eLife 12:e81320.
https://doi.org/10.7554/eLife.81320

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