| Literature DB >> 33586677 |
Alexandra C McQuattie-Pimentel1, Ziyou Ren1, Nikita Joshi1, Satoshi Watanabe1, Thomas Stoeger2, Monica Chi1, Ziyan Lu1, Lango Sichizya1, Raul Piseaux Aillon1, Ching-I Chen1, Saul Soberanes1, Zhangying Chen1, Paul A Reyfman1, James M Walter1, Kishore R Anekalla1, Jennifer M Davis1, Kathryn A Helmin1, Constance E Runyan1, Hiam Abdala-Valencia1, Kiwon Nam1, Angelo Y Meliton3, Deborah R Winter4, Richard I Morimoto5, Gökhan M Mutlu3, Ankit Bharat6, Harris Perlman4, Cara J Gottardi1, Karen M Ridge1, Navdeep S Chandel1, Jacob I Sznajder1, William E Balch7, Benjamin D Singer1,5, Alexander V Misharin1, G R Scott Budinger1.
Abstract
Alveolar macrophages orchestrate the response to viral infections. Age-related changes in these cells may underlie the differential severity of pneumonia in older patients. We performed an integrated analysis of single-cell RNA-Seq data that revealed homogenous age-related changes in the alveolar macrophage transcriptome in humans and mice. Using genetic lineage tracing with sequential injury, heterochronic adoptive transfer, and parabiosis, we found that the lung microenvironment drove an age-related resistance of alveolar macrophages to proliferation that persisted during influenza A viral infection. Ligand-receptor pair analysis localized these changes to the extracellular matrix, where hyaluronan was increased in aged animals and altered the proliferative response of bone marrow-derived macrophages to granulocyte macrophage colony-stimulating factor (GM-CSF). Our findings suggest that strategies targeting the aging lung microenvironment will be necessary to restore alveolar macrophage function in aging.Entities:
Keywords: Aging; Immunology; Influenza; Innate immunity; Macrophages
Mesh：
Year: 2021 PMID： 33586677 PMCID： PMC7919859 DOI： 10.1172/JCI140299
Source DB: PubMed Journal: J Clin Invest ISSN： 0021-9738 Impact factor: 14.808