Comparative dual transcriptome analysis of human macrophages infected with Crithidia-like or Leishmania parasites

Abstract

Human Visceral Leishmaniasis (VL) is a neglected disease caused by the two-host lifecycle protozoa parasite, Leishmania infantum, the parasite transmitted by sand fly bites of an infected female. VL can be lethal if untreated or treatments fail. VL is endemic in Brazil, showing a great focus on the Northeastern region, although recently it has spread across several regions of the country. Reports of leishmaniasis cases with co-infection with monoxenous trypanosomatid have been increasing annually. Previous genomic analysis demonstrated that clinical isolates from VL patients admitted at the Federal University Hospital in Sergipe, Brazil, don't belong to any Leishmania species and are closely related to the non-pathogenic Leishmaniinae parasite from genus Crithidia. We referred to this parasite as Crithidia-like. Here, our aim is to evaluate the difference in gene expression of human macrophage cell line infected with different Leishmania species and Crithidia-like strains through RNA sequencing (mRNA-seq). To the best of our knowledge, so far there are no transcriptome profile studies assessing in vitro infection of monoxenous versus dixenous trypanosomatid parasites. For this purpose, we will work in collaboration with Dr. Jesus G. Valenzuela and Dr. José M. Ribeiro at Vector Molecular Biology Section of National Institute of Allergy, and Infectious Diseases/National Institute of Health (NIAID/NIH), USA. The clinical isolates were obtained from atypical cases of VL (one fatal), in which the parasite strains were isolated from skin lesions and bone marrow aspirates. In this context, through dual RNA-seq, we simultaneously can identify the transcriptomic changes occurring both in the host and the parasites, leading in a dataset that will contribute to the understanding of the interaction between host and trypanosomatid parasites during intracellular infection. (AU)