Comparative transcriptome analysis of drug resistant clinical isolates of Leishmania infantum-infected human macrophages

Leishmaniasis is a neglected tropical parasitic disease with a worldwide distribution that can present a variety of clinical forms, depending on the parasite species and host genetic background. Chemotherapy is the only effective weapon whose effectiveness is limited by the frequent appearance of drug resistance and therapeutic failure; therefore, new therapeutic strategies are required. To increase the knowledge of factors contributing to drug resistance in leishmaniasis, we studied by RNA-seq the transcriptomic changes in the host THP-1 cells after infection with clinical Leishmania infantum isolates from leishmaniasis patients with different susceptibilities to anti-leishmanial drugs. Analysis of Differential Expression Genes (DEG) in infected host cells revealed a different number of DEG in the THP-1 infected cells according to the Leishmania line. One of the conclusions obtained is that the modulation of host cells is Leishmania-line dependent. GO enriched analyses of DEG indicated that some relevant biological processes were modulated in the infected host cells, specifically related to cellular metabolism, immune response, cellular defense response and signaling pathway, and cell proliferation and apoptosis. This study provided an overview of the THP-1 host transcriptomic changes that occurred after infection with drug resistant clinical isolates of L. infantum that could be associated with the parasite' s ability to evade host defenses and modulate the functions of the cells to survive intracellularly as well as to elude the toxic effects of anti-leishmanial drugs.