Impaired phagocytic function in CX3CR1+ tissue-resident skeletal muscle macrophages prevents muscle recovery after influenza A virus-induced pneumonia in old mice

Constance E. Runyan, Lynn C. Welch, Emilia Lecuona, Masahiko Shigemura, Luciano Amarelle, Hiam Abdala-Valencia, Nikita Joshi, Ziyan Lu, Kiwon Nam, Nikolay S. Markov, Alexandra C. McQuattie-Pimentel, Raul Piseaux-Aillon, Yuliya Politanska, Lango Sichizya, Satoshi Watanabe, Kinola J.N. Williams, G. R.Scott Budinger*, Jacob I. Sznajder, Alexander V. Misharin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Skeletal muscle dysfunction in survivors of pneumonia disproportionately affects older individuals in whom it causes substantial morbidity. We found that skeletal muscle recovery was impaired in old compared with young mice after influenza A virus-induced pneumonia. In young mice, recovery of muscle loss was associated with expansion of tissue-resident skeletal muscle macrophages and downregulation of MHC II expression, followed by a proliferation of muscle satellite cells. These findings were absent in old mice and in mice deficient in Cx3cr1. Transcriptomic profiling of tissue-resident skeletal muscle macrophages from old compared with young mice showed downregulation of pathways associated with phagocytosis and proteostasis, and persistent upregulation of inflammatory pathways. Consistently, skeletal muscle macrophages from old mice failed to downregulate MHCII expression during recovery from influenza A virus-induced pneumonia and showed impaired phagocytic function in vitro. Like old animals, mice deficient in the phagocytic receptor Mertk showed no macrophage expansion, MHCII downregulation, or satellite cell proliferation and failed to recover skeletal muscle function after influenza A pneumonia. Our data suggest that a loss of phagocytic function in a CX3CR1+ tissue-resident skeletal muscle macrophage population in old mice precludes satellite cell proliferation and recovery of skeletal muscle function after influenza A pneumonia.

Original languageEnglish (US)
Article numbere13180
JournalAging Cell
Volume19
Issue number9
DOIs
StatePublished - Sep 1 2020

Keywords

  • influenza
  • macrophages
  • pneumonia
  • skeletal muscle

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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