Impaired phagocytic function in CX3CR1 + tissue‐resident skeletal muscle macrophages prevents muscle recovery after influenza A virus‐induced pneumonia in old mice
Autor: | Nikita Joshi, Satoshi Watanabe, Emilia Lecuona, Kiwon Nam, Raul Piseaux-Aillon, G. R. Scott Budinger, Masahiko Shigemura, Kinola J.N. Williams, Nikolay S. Markov, Constance E. Runyan, Yuliya Politanska, Alexander V. Misharin, Luciano Amarelle, Jacob I. Sznajder, Hiam Abdala-Valencia, Alexandra C. McQuattie-Pimentel, Lango Sichizya, Ziyan Lu, Lynn C. Welch |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Aging Cell growth Phagocytosis Skeletal muscle Cell Biology MERTK Biology medicine.disease_cause 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Downregulation and upregulation CX3CR1 Immunology Influenza A virus medicine Receptor 030217 neurology & neurosurgery |
Zdroj: | Aging Cell. 19 |
ISSN: | 1474-9726 1474-9718 |
Popis: | 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. |
Databáze: | OpenAIRE |
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