Single-cell landscapes reveal a conserved IL-6-hepcidin axis coordinates renal antibacterial defense and immunopathology in Larimichthys crocea

The teleost kidney is a vital hematopoietic and secondary lymphoid organ, yet the cellular coordination and regulatory circuits driving its response to systemic infection remain poorly understood. Here, we present a high-resolution single-cell transcriptomic atlas of the large yellow croaker ( Larimichthys crocea ) kidney during challenge with the necrotizing pathogen Pseudomonas plecoglossicida . Our analysis reveals a profound remodeling of the renal immune microenvironment, characterized by a dramatic expansion of the myeloid compartment and the emergence of an integrated cell death signature, comprising apoptosis, ferroptosis, and necroptosis that underlies the formation of characteristic visceral white nodules. Through trajectory and RNA velocity analyses, we demonstrate that bacterial infection triggers “emergency granulopoiesis”, driving the rapid differentiation of neutrophils, macrophages and mast cells into hyper-inflammatory states. Crucially, we identify a non-canonical, multi-lineage antimicrobial response in which phagocytes serve as the primary sources of the antimicrobial peptide hepcidin, with selected activated B-cell and regulatory T-cell populations displaying additional hepcidin-associated signatures. We further establish the IL-6-JAK2/STAT3 signaling pathway as the master regulatory axis orchestrating this systemic defense. Pharmacological inhibition of JAK2 abolished hepcidin induction, while exogenous IL-6 administration significantly enhanced host survival and bacterial clearance. These findings delineate the evolutionary conservation of cytokine-mediated antimicrobial regulation and provide a comprehensive model of organ-level immune coordination in early vertebrates.