Long-term hematopoietic stem cells trigger quiescence in Leishmania parasites

by Laura Dirkx, Sara Van Acker, Yasmine Nicolaes, João Luís Reis Cunha, Rokaya Ahmad, Rik Hendrickx, Ben Caljon, Hideo Imamura, Didier G. Ebo, Daniel C. Jeffares, Yann G.-J. Sterckx, Louis Maes, Sarah Hendrickx, Guy Caljon

Addressing the challenges of quiescence and post-treatment relapse is of utmost importance in the microbiology field. This study shows that Leishmania infantum and L. donovani parasites rapidly enter into quiescence after an estimated 2–3 divisions in both human and mouse bone marrow stem cells. Interestingly, this behavior is not observed in macrophages, which are the primary host cells of the Leishmania parasite. Transcriptional comparison of the quiescent and non-quiescent metabolic states confirmed the overall decrease of gene expression as a hallmark of quiescence. Quiescent amastigotes display a reduced size and signs of a rapid evolutionary adaptation response with genetic alterations. Our study provides further evidence that this quiescent state significantly enhances resistance to treatment. Moreover, transitioning through quiescence is highly compatible with sand fly transmission and increases the potential of parasites to infect cells. Collectively, this work identified stem cells in the bone marrow as a niche where Leishmania quiescence occurs, with important implications for antiparasitic treatment and acquisition of virulence traits.