A quest for mechanisms and biomarkers of post-treatment relapse during visceral leishmaniasis.

In the last decade, stem cells have been discovered to serve as a reservoir for many pathogenic organisms. Our recent research on visceral leishmaniasis (VL) revealed that hematopoietic stem cells (HSC) in the bone marrow underlie treatment failure and relapse. These cells exhibit a unique transcriptional signature (StemLeish) and provide an environment for the development of parasite quiescence, a metabolic state that is impervious to drug treatment. This project will build upon these cutting-edge findings in order to obtain (i) a thorough characterization of immunological processes in the HSC niche that are at the basis of treatment failure, and (ii) mechanistic insights in the possible trigger(s) of VL relapse and the particular role of Macrophage Migration Inhibitory Factor (MIF). From an applied research viewpoint, this project will (iii) establish the diagnostic value of HSC biomarkers using patient samples and (iv) install a novel drug screening platform based on the developed tools to predict and capture the risk of relapse. It is expected that this project will open new therapeutic avenues that may extend beyond leishmaniasis and be revolutionary in the precarious battle against treatment failure.

Keywords:INFECTIONS, PARASITOLOGY, IMMUNOLOGY

Disciplines:Transcriptomics, Adaptive immunology, Infectious diseases, Parasitology