A single-cell transcriptomic atlas of peripheral blood immune cells spanning progressive canine leishmaniosis

Abstract

Dogs play a major role in sustaining transmission of Leishmania infantum to people, thus prevention and treatment of canine leishmaniosis (CanL) to reduce transmission represents an unmet public health need. Although advances have been made in understanding how immunopathology correlates to infectiousness as CanL progresses, the immune mechanisms underlying transition between disease stages and terminal decline remain ill-defined. To address this knowledge gap, we generated a comprehensive atlas of peripheral immune cells from control dogs and naturally-infected dogs using single-cell RNA sequencing. The LeishDog Atlas captures the cellular and transcriptional complexity underlying CanL, tracing shifts in immune composition and gene expression across progressive, well-defined disease stages. Notably, we identified distinct myeloid, CD4+ and CD8+ T cell phenotypes and transcriptional states associated with disease progression. This resource provides a valuable framework for understanding systemic immune dysregulation in CanL, including determinants of T cell exhaustion and myeloid cell activation, and establishes a foundation for comparative, translational, and mechanistic studies of CanL immunopathology and transmissibility.