Despite the prevalence and clinical importance of influenza, its long-term effect on lung immunity is unclear. Here we describe that following viral clearance and clinical recovery, at 1 month after infection with influenza, mice are better protected from Streptococcus pneumoniae infection due to a population of monocyte-derived alveolar macrophages (AMs) that produce increased interleukin-6. Influenza-induced monocyte-derived AMs have a surface phenotype similar to resident AMs but display a unique functional, transcriptional and epigenetic profile that is distinct from resident AMs. In contrast, influenza-experienced resident AMs remain largely similar to naive AMs. Thus, influenza changes the composition of the AM population to provide prolonged antibacterial protection. Monocyte-derived AMs persist over time but lose their protective profile. Our results help to understand how transient respiratory infections, a common occurrence in human life, can constantly alter lung immunity by contributing monocyte-derived, recruited cells to the AM population.
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Sequencing data are available in GEO under accession code GSE120543.
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We are grateful to S. Rose-John (Kiel University) for the kind gift of anti-IL-6, to C. Reis e Sousa and G. Stockinger for reading the manuscript and A. Warnatsch for initial help with reactive oxygen species measurements. This work benefited from data assembled by the ImmGen consortium. We thank the Advanced Sequencing, Flow Cytometry, Biological Research and Histopathology facilities of the Francis Crick Institute for excellent support. This study was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001206), the UK Medical Research Council (FC001206) and the Wellcome Trust (FC001206). Support by MRC grant U117597139 (S.C. and A.W.) and a BBSRC-GSK-funded case studentship BB/L502315/1 (H.A.) is gratefully acknowledged.
E.M.H. and S.B. were employees of GSK at the time of this study. The other authors declare that they have no conflict of interest.
Peer review information Zoltan Fehervari was the primary editor on this article and managed its editorial process and peer review in collaboration with the rest of the editorial team.
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Aegerter, H., Kulikauskaite, J., Crotta, S. et al. Influenza-induced monocyte-derived alveolar macrophages confer prolonged antibacterial protection. Nat Immunol 21, 145–157 (2020). https://doi.org/10.1038/s41590-019-0568-x