Tissue-specific transcriptomic changes associated with AmBisome treatment of mice with experimental visceral leishmaniasis

RNAseq of mouse liver and spleen samples infected with M. bovis treated with ambisome Liposomal amphotericin B (AmBisome) is a commonly used treatment for visceral leishmaniasis (VL), but is significantly less effective in the treatment of VL in East Africa, where the burden of disease is now greatest. Despite its widespread use, little is known of the mode of action of AmBisome. Here, we sought to examine the impact of AmBisome on tissue-specific transcriptomic changes following experimental infection with Leishmania donovani, in the two most clinically important tissues for treatment, the spleen and the liver. BALB/c mice infected with M. bovis BCG (an organism resistant to AmBisome treatment) were used to distinguish between direct effects of AmBisome and those that are secondary to parasite death using the RNAseq libraries generated to compare to previously published transcriptomic data of Leishmania donovani infected spleen and liver tissues treated with AmBisome. Our data indicate that the tissue response to AmBisome treatment is varied in different target organs and that full restoration of homeostasis is not achieved at parasitological cure. The pathways required to restore homeostasis deserve fuller attention in order to understand mechanisms associated with treatment failure and relapse and to promote more rapid restoration of immune competence. Overall design: 10 6-8 week old BALB/c mice infected with BCG-SSI. At 35 days post infected, 5 were treated with Ambisome. All mice were culled at d42 and whole RNA isolated from tissues collected from this time point