Single-cell analysis reveals lasting immunological consequences of influenza infection and respiratory immunization in the pig lung
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
The pig is a natural host for influenza viruses and integrally involved in virus evolution through interspecies transmissions between humans and swine. Swine have many physiological, anatomical, and immunological similarities to humans, and are an excellent model for human influenza. Here, we employed single cell RNA-sequencing (scRNA-seq) and flow cytometry to characterize the major leukocyte subsets in bronchoalveolar lavage (BAL), twenty-one days after H1N1pdm09 infection or respiratory immunization with an adenoviral vector vaccine expressing hemagglutinin and nucleoprotein with or without IL-1β. Mapping scRNA-seq clusters from BAL onto those previously described in peripheral blood facilitated annotation and highlighted differences between tissue resident and circulating immune cells. ScRNA-seq data and functional assays revealed lasting impacts of immune challenge on BAL populations. First, mucosal administration of IL-1β reduced the number of functionally active Treg cells. Second, influenza infection upregulated IFI6 in BAL cells and decreased their susceptibility to virus replication in vitro. Our data provide a reference map of porcine BAL cells and reveal lasting immunological consequences of influenza infection and respiratory immunization in a highly relevant large animal model for respiratory virus infection.
Date Issued
2024-07
Date Acceptance
2024-06-07
Citation
PLoS Pathogens, 2024, 20 (7)
ISSN
1553-7366
Publisher
Public Library of Science (PLoS)
Journal / Book Title
PLoS Pathogens
Volume
20
Issue
7
Copyright Statement
© 2024 Muir 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.
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.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/39024231
Subjects
Animals
Bronchoalveolar Lavage Fluid
Immunization
Influenza A Virus, H1N1 Subtype
Influenza Vaccines
Lung
Orthomyxoviridae Infections
Single-Cell Analysis
Swine
Publication Status
Published
Coverage Spatial
United States
Article Number
e1011910
Date Publish Online
2024-07-18