Persistent myeloid cell reprogramming despite miltefosine treatment in leishmania-infected macaques
Abstract
Visceral leishmaniasis (VL) is a neglected tropical disease caused by protozoan parasites. An inflammatory immune response, associated with tissue injury, occurs shortly after infection. Using a rhesus macaque model of VL, we evaluated the impact of miltefosine therapy administered during the acute phase of infection. Despite therapy, parasites persist in multiple tissues, including the spleen, bone marrow, peripheral, and mesenteric lymph nodes. Parasite burden inversely correlates with cellular miltefosine levels. Notably, L. infantum remains detectable three months post-treatment. Single-cell transcriptomic analysis reveals cellular heterogeneity and reprogramming of splenic myeloid cells post-treatment, including inflammatory macrophages, immature plasmacytoid dendritic cells, and type 2 dendritic cells (DCs). Flow cytometric sorting of splenic neutrophils, macrophages, and DCs confirms the presence of L. infantum post-treatment, highlighting the challenge of parasite clearance. Our findings reveal a disrupted innate immune landscape post-infection that persists after treatment, indicating myeloid cell reprogramming may sustain chronic infection and parasite persistence.
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BibTeX
@article{picard2026persistent,
title = {{Persistent myeloid cell reprogramming despite miltefosine treatment in leishmania-infected macaques}},
author = {Morgane Picard and Steven Boutrais and Vasco Rodrigues and Yasmina Fortier and Chloé Borde and Calaiselvy Soundaramourty and Julien Clain and Charles Joly-Beauparlant and Gina Racine and Ouafa Zghidi-Abouzid and Arnaud Droit and Alain Pruvost and Maria Paola Costi and Ricardo Silvestre and Anabela Cordeiro da Silva and Jane Macdougall and Sónia André and Jérôme Estaquier},
journal = {iScience},
year = {2026},
month = aug,
doi = {10.1016/j.isci.2025.113900},
url = {https://hal.inrae.fr/hal-05706475v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Persistent myeloid cell reprogramming despite miltefosine treatment in leishmania-infected macaques
AU - Morgane Picard
AU - Steven Boutrais
AU - Vasco Rodrigues
AU - Yasmina Fortier
AU - Chloé Borde
AU - Calaiselvy Soundaramourty
AU - Julien Clain
AU - Charles Joly-Beauparlant
AU - Gina Racine
AU - Ouafa Zghidi-Abouzid
AU - Arnaud Droit
AU - Alain Pruvost
AU - Maria Paola Costi
AU - Ricardo Silvestre
AU - Anabela Cordeiro da Silva
AU - Jane Macdougall
AU - Sónia André
AU - Jérôme Estaquier
PY - 2026
DA - 2026/08/31
JO - iScience
DO - 10.1016/j.isci.2025.113900
UR - https://hal.inrae.fr/hal-05706475v1
AB - Visceral leishmaniasis (VL) is a neglected tropical disease caused by protozoan parasites. An inflammatory immune response, associated with tissue injury, occurs shortly after infection. Using a rhesus macaque model of VL, we evaluated the impact of miltefosine therapy administered during the acute phase of infection. Despite therapy, parasites persist in multiple tissues, including the spleen, bone marrow, peripheral, and mesenteric lymph nodes. Parasite burden inversely correlates with cellular miltefosine levels. Notably, L. infantum remains detectable three months post-treatment. Single-cell transcriptomic analysis reveals cellular heterogeneity and reprogramming of splenic myeloid cells post-treatment, including inflammatory macrophages, immature plasmacytoid dendritic cells, and type 2 dendritic cells (DCs). Flow cytometric sorting of splenic neutrophils, macrophages, and DCs confirms the presence of L. infantum post-treatment, highlighting the challenge of parasite clearance. Our findings reveal a disrupted innate immune landscape post-infection that persists after treatment, indicating myeloid cell reprogramming may sustain chronic infection and parasite persistence.
SN - 2589-0042
ER -