An integrated single-cell, spatial, and bulk transcriptomic atlas of the immune response to Nocardia seriolae infection in largemouth bass (Micropterus salmoides)

Granulomas are evolutionarily conserved, macrophage-driven immune structures that form to wall off persistent pathogens, representing a core pathological hallmark in major human diseases like tuberculosis. The evolutionary origins of these complex structures are rooted in teleost fish, making them a critical model system for understanding a fundamental principle of vertebrate immunity. While zebrafish models have offered initial insights, we utilize the Largemouth Bass (Micropterus salmoides), a natural host for Nocardia seriolae, as a platform that allows for the study of complex, large-scale granulomas that more closely recapitulate chronic pathology. Despite its importance, the core molecular programs driving granuloma formation and long-term maintenance remain poorly understood. To address this, our project undertakes a systems-level analysis combining spatial transcriptomics and single-cell RNA sequencing (scRNA-seq) of head kidney tissues with bulk RNA-seq of eight key organs (liver, spleen, kidney, head kidney, gill, intestine, brain, and muscle) from both healthy and Nocardia seriolae-infected bass. This study aims to provide the first comprehensive molecular blueprint of this ancient immune structure. We specifically focus on defining its cellular basis, core regulatory networks, and maintenance mechanisms, ultimately revealing novel insights into the fundamental design principles of vertebrate granulomatous immunity.