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:10.1016/j.isci.2026.116870

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

Journal article

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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

iScience, Vol.29(8), 116870

08/21/2026

DOI: 10.1016/j.isci.2026.116870

PMCID: PMC13444607

PMID: 42564585

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Abstract

Dogs play a major role in sustaining the transmission of Leishmania infantum to people, making prevention and treatment of canine leishmaniosis (CanL) public health priorities. However, immune mechanisms underlying progression from subclinical stages to terminal disease in dogs remain ill-defined. To address this gap, we generated a single-cell RNA sequencing map of peripheral immune cells from uninfected and naturally infected dogs across well-defined stages of L. infantum infection. Disease progression was marked by a shift from a lymphoid-to a myeloid-dominated immune landscape. CD4+ T cells transition from naive to effector states, with TH1 cells showing progressive exhaustion signatures paralleling disease progression, while CD8+ T cells exhibited TPEX-like phenotypes with differentiation toward effector and proliferative programs during severe L. infantum infection. Monocytes showed inflammatory remodeling across clinical stages. The LeishDog Atlas provides a framework for understanding immune dysregulation in CanL and a resource for comparative and translational studies of its immunopathology. [Display omitted] •Disease progression shifts the immune landscape from lymphoid to myeloid•CD4+ TH1 cells exhibit increased exhaustion markers as disease progresses•CD8+ T cells follow progenitor exhaustion trajectories in severe CanL•Monocytes show dynamic inflammatory remodeling during disease progression Genomics; Immunology

canine leishmaniosis

dog immune cell atlas

scRNA-seq

visceral leishmaniasis

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 - Hull York Medical School
Max C Waugh - The Ohio State University
Shoumit Dey - Hull York Medical School
Najmeeyah Brown - Hull York Medical School
Karen I. Cyndari - University of Iowa
Jacob J. Oleson - University of Iowa
Paul M. Kaye - Hull York Medical School
Christine A. Petersen - The Ohio State University
Resource Type: Journal article
Publication Details: iScience, Vol.29(8), 116870
DOI: 10.1016/j.isci.2026.116870
PMID: 42564585
PMCID: PMC13444607
ISSN: 2589-0042
eISSN: 2589-0042
Publisher: Elsevier Inc
Grant note: National Institutes of Health (NIH): R01AI171971 Wellcome Investigator Award: 224290
This work was supported by the National Institutes of Health (NIH) (grant no. R01AI171971) . P.M.K. is also supported by a Wellcome Investigator Award (#224290) . The authors thank the animal caretakers who participated in the study, Sally James and Lesley Gilbert (Biosciences Technology Facility, University of York) for technical assistance, as well as Alastair Droop (Biosciences Technology Facility, University of York) and Nidhi Dey for advice on analytical approaches. Elements of the graphical abstract were created with BioRender.com. Uhl, D. (2026) https://BioRender.com/f0gkvad.
Language: English
Date published: 08/21/2026
Academic Unit: Epidemiology; Emergency Medicine; Biostatistics; Orthopedics and Rehabilitation; Obstetrics and Gynecology; Otolaryngology; Internal Medicine
Record Identifier: 9985214917102771

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