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Infection and chronic disease activate a systemic brain-muscle signaling axis.
- Source :
-
Science immunology [Sci Immunol] 2024 Jul 12; Vol. 9 (97), pp. eadm7908. Date of Electronic Publication: 2024 Jul 12. - Publication Year :
- 2024
-
Abstract
- Infections and neurodegenerative diseases induce neuroinflammation, but affected individuals often show nonneural symptoms including muscle pain and muscle fatigue. The molecular pathways by which neuroinflammation causes pathologies outside the central nervous system (CNS) are poorly understood. We developed multiple models to investigate the impact of CNS stressors on motor function and found that Escherichia coli infections and SARS-CoV-2 protein expression caused reactive oxygen species (ROS) to accumulate in the brain. ROS induced expression of the cytokine Unpaired 3 (Upd3) in Drosophila and its ortholog, IL-6, in mice. CNS-derived Upd3/IL-6 activated the JAK-STAT pathway in skeletal muscle, which caused muscle mitochondrial dysfunction and impaired motor function. We observed similar phenotypes after expressing toxic amyloid-β (Aβ42) in the CNS. Infection and chronic disease therefore activate a systemic brain-muscle signaling axis in which CNS-derived cytokines bypass the connectome and directly regulate muscle physiology, highlighting IL-6 as a therapeutic target to treat disease-associated muscle dysfunction.
- Subjects :
- Animals
Mice
Chronic Disease
Interleukin-6 metabolism
Interleukin-6 immunology
Escherichia coli Infections immunology
Reactive Oxygen Species metabolism
Reactive Oxygen Species immunology
Drosophila Proteins metabolism
Drosophila Proteins immunology
Drosophila Proteins genetics
SARS-CoV-2 immunology
Drosophila melanogaster immunology
Amyloid beta-Peptides metabolism
Humans
Mice, Inbred C57BL
Brain immunology
Brain metabolism
Signal Transduction immunology
Muscle, Skeletal immunology
Muscle, Skeletal metabolism
COVID-19 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2470-9468
- Volume :
- 9
- Issue :
- 97
- Database :
- MEDLINE
- Journal :
- Science immunology
- Publication Type :
- Academic Journal
- Accession number :
- 38996009
- Full Text :
- https://doi.org/10.1126/sciimmunol.adm7908