Single-cell analysis reveals lasting immunological consequences of influenza infection and respiratory immunization in the pig lung

• DOI: 10.1371/journal.ppat.1011910
• Publication Date: 2024-07-18T17:22:04Z
• Authors: Andrew Muir; Basudev Paudyal; Selma Schmidt; Ehsan Sedaghat-Ro...; Soumendu Chakravarti; Sonia Villanueva-...; Katy Moffat; Noemi Polo; Nicos Angelopoulos; Anna Schmidt; Matthias Tenbusch; Graham Freimanis; Wilhelm Gerner; Arianne C. Richard; Elma Tchilian
• Keywords: 570; QH301-705.5; Swine; RC581-607; 630; Influenza A Virus, H1N1 Subtype; Orthomyxoviridae Infections; Influenza Vaccines; Animals; Immunization; Immunologic diseases. Allergy; Biology (General); Single-Cell Analysis; Lung; Bronchoalveolar Lavage Fluid; Research Article

The pig is a natural host for influenza viruses and integrally involved in virus evolution through interspecies transmissions between humans swine. Swine have many physiological, anatomical, immunological similarities to humans, are an excellent model human influenza. Here, we employed single cell RNA-sequencing (scRNA-seq) flow cytometry characterize the major leukocyte subsets bronchoalveolar lavage (BAL), twenty-one days after H1N1pdm09 infection or respiratory immunization with adenoviral vector vaccine expressing hemagglutinin nucleoprotein without IL-1β. Mapping scRNA-seq clusters from BAL onto those previously described peripheral blood facilitated annotation highlighted differences tissue resident circulating immune cells. ScRNA-seq data functional assays revealed lasting impacts of challenge on populations. First, mucosal administration IL-1β reduced number functionally active Treg Second, upregulated IFI6 cells decreased their susceptibility replication vitro . Our provide reference map porcine reveal consequences highly relevant large animal infection.