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

Danielle P Uhl; Daniel J Holbrook; Max C Waugh; Shoumit Dey; Najmeeyah Brown; Karen I Cyndari; Jacob J Oleson; Paul M Kaye; Christine A Petersen

doi:10.64898/2025.12.18.695149

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

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

Danielle P Uhl, Daniel J Holbrook, Max C Waugh, Shoumit Dey, Najmeeyah Brown, Karen I Cyndari, Jacob J Oleson, Paul M Kaye and Christine A Petersen

bioRxiv

Cold Spring Harbor Laboratory

12/21/2025

DOI: 10.64898/2025.12.18.695149

PMCID: PMC12724653

PMID: 41446132

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https://doi.org/10.64898/2025.12.18.695149View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

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.

Details

Title: Subtitle: A single-cell transcriptomic atlas of peripheral blood immune cells spanning progressive canine leishmaniosis
Creators: Danielle P Uhl - University of Iowa
Daniel J Holbrook - University of York
Max C Waugh - The Ohio State University
Shoumit Dey - University of York
Najmeeyah Brown - University of York
Karen I Cyndari - University of Iowa
Jacob J Oleson - University of Iowa
Paul M Kaye - University of York
Christine A Petersen - The Ohio State University
Resource Type: Preprint
Publication Details: bioRxiv
DOI: 10.64898/2025.12.18.695149
PMID: 41446132
PMCID: PMC12724653
NLM abbreviation: bioRxiv
ISSN: 2692-8205
eISSN: 2692-8205
Publisher: Cold Spring Harbor Laboratory; United States
Language: English
Date posted: 12/21/2025
Academic Unit: Epidemiology; Emergency Medicine; Biostatistics; Orthopedics and Rehabilitation; Obstetrics and Gynecology; Otolaryngology; Internal Medicine
Record Identifier: 9985096040002771

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