Identification of a nerve-associated, lung-resident interstitial macrophage subset with distinct localization and immunoregulatory properties
- 13 March 2020
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Immunology
- Vol. 5 (45)
- https://doi.org/10.1126/sciimmunol.aax8756
Abstract
Tissue-resident macrophages are a diverse population of cells that perform specialized functions including sustaining tissue homeostasis and tissue surveillance. Here, we report an interstitial subset of CD169+ lung-resident macrophages that are transcriptionally and developmentally distinct from alveolar macrophages (AMs). They are primarily localized around the airways and are found in close proximity to the sympathetic nerves in the bronchovascular bundle. These nerve- and airway-associated macrophages (NAMs) are tissue resident, yolk sac derived, self-renewing, and do not require CCR2+ monocytes for development or maintenance. Unlike AMs, the development of NAMs requires CSF1 but not GM-CSF. Bulk population and single-cell transcriptome analysis indicated that NAMs are distinct from other lung-resident macrophage subsets and highly express immunoregulatory genes under steady-state and inflammatory conditions. NAMs proliferated robustly after influenza infection and activation with the TLR3 ligand poly(I:C), and in their absence, the inflammatory response was augmented, resulting in excessive production of inflammatory cytokines and innate immune cell infiltration. Overall, our study provides insights into a distinct subset of airway-associated pulmonary macrophages that function to maintain immune and tissue homeostasis.Keywords
Funding Information
- National Heart, Lung, and Blood Institute (R01HL084312)
- National Cancer Institute (CA232666)
- National Institute of Allergy and Infectious Diseases (R01AI143861)
- National Institute of Allergy and Infectious Diseases (AG049074)
- National Institute of Allergy and Infectious Diseases (AI097375)
- National Institute of Allergy and Infectious Diseases (R01AI33977)
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