Single-cell transcriptomics reveals altered myeloid cell profiles associated with the early establishment of leishmania reservoirs

Abstract

Abstract Current drug regimens to treat visceral leishmaniasis (VL) are associated with a significant frequency of infection relapses, particularly in immunosuppressed patients. Understanding the cellular and tissue-specific persistence of Leishmania infantum post-treatment is crucial for improving therapeutic outcomes. Using a rhesus macaque model of VL, despite the administration of miltefosine (HePC) shortly after infection, L. infantum was detected in various tissues, including the spleen, bone marrow, and peripheral and mesenteric lymph nodes (LNs). Notably, lower HePC penetration in pLNs correlated with persistent parasites, culminating in mLNs relapse three months post-treatment. Our analysis of splenic neutrophils, monocytes/macrophages, and dendritic cells post-HePC treatment revealed parasite reservoirs. Single-cell transcriptomic analysis unveiled myeloid cell heterogeneity and indicated a correlation between the failure to eradicate parasites and incomplete immune cell restoration in the spleen. This study provides valuable insights for developing more effective treatments targeting parasite reservoirs that potentially may reduce relapses.