articleNature CommunicationsJan 7, 2026GOLD OA

Chronic macrophage activation derails muscle repair by disrupting mannose-receptor-linked plasticity revealed by endogenous irg1/acod1 tracking

CGCaroline G. SpencerMHMatthew HamiltonEBEthan BedsoleYNYingshan N. WeiAMAlison M. Rojas

University of North Carolina at Chapel Hill

PubMed
Indexed incrossrefdoajpubmed

Abstract

Macrophages are central drivers of chronic inflammation, yet how a sustained inflammatory state alters their function remains unclear. Using GFP knock-in zebrafish targeting irg1/acod1 that marks macrophage activation, we track the dynamic transitions of macrophage states during acute muscle injury under homeostatic and chronically inflamed conditions, induced by genetic mutation of nlrc3l. In the chronic inflammation model, muscle repair is impaired and expression of the mannose receptor mrc1b/cd206 is severely downregulated in a myd88-dependent manner. Two reparative macrophage subtypes, defined by their cellular behavior and single-cell transcriptomics profile, clustering and muscle-encasing, are lost. A…

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Topics & keywords

Topics
Keywords
  • Macrophage
  • Inflammation
  • Zebrafish
  • M2 Macrophage
  • Macrophage polarization
  • Downregulation and upregulation
  • Transcriptome
  • Intracellular
UN Sustainable Development Goals
  • Good health and well-being
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