Cellular and molecular dynamics in the lungs of neonatal and juvenile mice in response to E. coli

  1. Sharon A McGrath-Morrow  Is a corresponding author
  2. Jarrett Venezia
  3. Roland Ndeh
  4. Nigel Michki
  5. Javier Perez
  6. Benjamin David Singer
  7. Raffaello Cimbro
  8. Mark Soloski
  9. Alan L Scott
  1. Children's Hospital of Philadelphia, United States
  2. Johns Hopkins University, United States
  3. Northwestern University, United States

Abstract

Bacterial pneumonia in neonates can cause significant morbidity and mortality when compared to other childhood age groups. To understand the immune mechanisms that underlie these age-related differences, we employed a mouse model of E. coli pneumonia to determine the dynamic cellular and molecular differences in immune responsiveness between neonates (PND 3-5) and juveniles (PND 12-18), at 24, 48, and 72 hours. Cytokine gene expression from whole lung extracts was also quantified at these time points, using qRT-PCR. E. coli challenge resulted in rapid and significant increases in neutrophils, monocytes, and γδT cells, along with significant decreases in dendritic cells and alveolar macrophages in the lungs of both neonates and juveniles. E. coli challenged juvenile lung had significant increases in interstitial macrophages and recruited monocytes that were not observed in neonatal lungs. Expression of IFNg-responsive genes was positively correlated with the levels and dynamics of MHCII-expressing innate cells in neonatal and juvenile lungs. Several facets of immune responsiveness in the wild-type neonates were recapitulated in juvenile MHCII-/- juveniles. Employing a pre-clinical model of E. coli pneumonia, we identified significant differences in the early cellular and molecular dynamics in the lungs that likely contribute to the elevated susceptibility of neonates to bacterial pneumonia and could represent targets for intervention to improve respiratory outcomes and survivability of neonates.

Data availability

Data generated for this study are available through the FlowRepository archive (https://flowrepository.org) under accession numbers FR-FCM-Z63A and FR-FCM-Z63B

Article and author information

Author details

  1. Sharon A McGrath-Morrow

    Division of Pulmonary Medicine and Sleep, Children's Hospital of Philadelphia, Philadelphia, United States
    For correspondence
    mcgrathmos@chop.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1576-5394
  2. Jarrett Venezia

    W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8736-0775
  3. Roland Ndeh

    Division of Pulmonary Medicine and Sleep, Children's Hospital of Philadelphia, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Nigel Michki

    Division of Pulmonary Medicine and Sleep, Children's Hospital of Philadelphia, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Javier Perez

    Division of Pulmonary Medicine and Sleep, Children's Hospital of Philadelphia, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Benjamin David Singer

    Department of Medicine, Northwestern University, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5775-8427
  7. Raffaello Cimbro

    Department of Medicine, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Mark Soloski

    Department of Medicine, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Alan L Scott

    W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0834-728X

Funding

National Heart, Lung, and Blood Institute (HL114800)

  • Sharon A McGrath-Morrow

National Heart, Lung, and Blood Institute (HL-140623)

  • Alan L Scott

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

Reviewing Editor

  1. Paul W Noble, Cedars-Sinai Medical Center, United States

Ethics

Animal experimentation: All experiments were conducted in accordance with the standards established by the United States Animal Welfare Acts, set forth in NIH guidelines and the Policy and Procedures Manual of the Johns Hopkins University Animal Care and Use Committee (ACUC), protocol # MO16M213.

Version history

  1. Received: August 24, 2022
  2. Preprint posted: September 21, 2022 (view preprint)
  3. Accepted: June 1, 2023
  4. Accepted Manuscript published: June 2, 2023 (version 1)
  5. Version of Record published: June 13, 2023 (version 2)

Copyright

© 2023, McGrath-Morrow 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. Sharon A McGrath-Morrow
  2. Jarrett Venezia
  3. Roland Ndeh
  4. Nigel Michki
  5. Javier Perez
  6. Benjamin David Singer
  7. Raffaello Cimbro
  8. Mark Soloski
  9. Alan L Scott
(2023)
Cellular and molecular dynamics in the lungs of neonatal and juvenile mice in response to E. coli
eLife 12:e82933.
https://doi.org/10.7554/eLife.82933

Share this article

https://doi.org/10.7554/eLife.82933

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