- Research Article
1
- 10.1016/j.fsi.2026.111287
Single-cell sequencing reveals metabolic reprogramming and immune regulation underlie the maintenance of teleost granulomas.
- Jun 01, 2026
- Fish & shellfish immunology
- Zheng-Yang Zhou + 17 more +17
The granuloma serves not only as a physical barrier to restrict the dissemination of intracellular pathogens but also functions as a complex immune microenvironment. However, the bioenergetics and regulatory mechanisms maintaining this architecture remain elusive in vertebrates. Here, integrating multi-tissue transcriptomics, single-cell RNA sequencing (scRNA-seq), ultrastructural imaging, and fluorescence in situ hybridization (FISH) in a largemouth bass (Micropterus salmoides)-Nocardia seriolae infection model, we resolved the metabolic and functional landscape of the granuloma. We found that across multiple tissues (head kidney, spleen, liver, kidney), the host initiates a synchronized transcriptional program that promotes macrophage differentiation into specialized epithelioid macrophages (E-Macs). Notably, E-Macs concurrently upregulated specific transporters and metabolic enzymes (e.g., laao, slc6a8), as well as oxidative phosphorylation (OXPHOS) and glycolysis genes, accompanied by mitochondrial proliferation. Functionally, E-Macs shifted from a pro-inflammatory to an immunoregulatory and pro-survival phenotype, characterized by high expression of protease inhibitors (e.g., csta) and anti-apoptotic factors (e.g., bcl2l14, ywhag1). Comparative analysis in zebrafish confirmed these metabolic and regulatory signatures are evolutionarily conserved. In conclusion, this study reveals a host survival strategy of immune regulation underpinned by metabolic adaptation, providing novel perspectives for controlling chronic granulomatous diseases in aquaculture.
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