Cellular and molecular dynamics in the lungs of neonatal and juvenile mice in response to E. coli
- Children's Hospital of Philadelphia, United States
- Johns Hopkins University, United States
- 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
Sharon A McGrath-Morrow
Benjamin David Singer
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
- 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
- Received: August 24, 2022
- Preprint posted: September 21, 2022 (view preprint)
- Accepted: June 1, 2023
- Accepted Manuscript published: June 2, 2023 (version 1)
- 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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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
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