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The lung microenvironment shapes a dysfunctional response of alveolar macrophages in aging.
McQuattie-Pimentel, Alexandra C; Ren, Ziyou; Joshi, Nikita; Watanabe, Satoshi; Stoeger, Thomas; Chi, Monica; Lu, Ziyan; Sichizya, Lango; Aillon, Raul Piseaux; Chen, Ching-I; Soberanes, Saul; Chen, Zhangying; Reyfman, Paul A; Walter, James M; Anekalla, Kishore R; Davis, Jennifer M; Helmin, Kathryn A; Runyan, Constance E; Abdala-Valencia, Hiam; Nam, Kiwon; Meliton, Angelo Y; Winter, Deborah R; Morimoto, Richard I; Mutlu, Gökhan M; Bharat, Ankit; Perlman, Harris; Gottardi, Cara J; Ridge, Karen M; Chandel, Navdeep S; Sznajder, Jacob I; Balch, William E; Singer, Benjamin D; Misharin, Alexander V; Budinger, G R Scott.
  • McQuattie-Pimentel AC; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
  • Ren Z; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
  • Joshi N; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
  • Watanabe S; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
  • Stoeger T; Department of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois, USA.
  • Chi M; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
  • Lu Z; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
  • Sichizya L; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
  • Aillon RP; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
  • Chen CI; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
  • Soberanes S; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
  • Chen Z; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
  • Reyfman PA; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
  • Walter JM; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
  • Anekalla KR; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
  • Davis JM; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
  • Helmin KA; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
  • Runyan CE; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
  • Abdala-Valencia H; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
  • Nam K; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
  • Meliton AY; Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Chicago Hospitals, Chicago, Illinois, USA.
  • Winter DR; Department of Medicine, Division of Rheumatology, Northwestern University, Chicago, Illinois, USA.
  • Morimoto RI; Department of Biochemistry and Molecular Genetics, Northwestern University, Evanston, Illinois, USA.
  • Mutlu GM; Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Chicago Hospitals, Chicago, Illinois, USA.
  • Bharat A; Department of Surgery, Division of Thoracic Surgery, Northwestern University, Chicago, Illinois, USA.
  • Perlman H; Department of Medicine, Division of Rheumatology, Northwestern University, Chicago, Illinois, USA.
  • Gottardi CJ; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
  • Ridge KM; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
  • Chandel NS; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
  • Sznajder JI; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
  • Balch WE; The Scripps Research Institute Department of Chemical Physiology, La Jolla, California, USA.
  • Singer BD; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
  • Misharin AV; Department of Biochemistry and Molecular Genetics, Northwestern University, Evanston, Illinois, USA.
  • Budinger GRS; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.
J Clin Invest ; 131(4)2021 02 15.
Article in English | MEDLINE | ID: covidwho-1172781
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Aging / Macrophages, Alveolar / Cellular Microenvironment / Lung Type of study: Prognostic study Limits: Animals / Humans Language: English Year: 2021 Document Type: Article Affiliation country: JCI140299

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Aging / Macrophages, Alveolar / Cellular Microenvironment / Lung Type of study: Prognostic study Limits: Animals / Humans Language: English Year: 2021 Document Type: Article Affiliation country: JCI140299