Abstract
Visceral leishmaniasis (VL) is a serious and fatal disease. Therapeutic drugs are toxic and non-sterilizing. The etiological agents Leishmania infantum and Leishmania donovani cause active and asymptomatic diseases. Effective drugs to treat VL exist but unfortunately, post-treatment relapses are common. Little is known why drugs are non-sterilizing or how these intracellular pathogens can escape treatment. Here, using a murine model of VL we found that CD271+/Sca1+ bone marrow mesenchymal stem cells (BM-MSCs) are readily infected in vitro and in vivo by L. infantum. Because BM-MSCs express potent drug efflux pumps, e.g., ABCG2 it is possible that this unique intracellular infectious niche could allow L. infantum to escape anti-parasite drugs.
Highlights
Visceral leishmaniasis (VL) is caused by Leishmania donovani-complex organisms and is endemic in the tropical and subtropical areas of the World
CD271+ bone marrow mesenchymal stem cells (BM-Mesenchymal stem cells (MSC)) as a Unique Infectious Niche for L. infantum one half of the cultures were removed from the chambers followed by washing and staining for Flow Cytometry analysis
These results suggest that, like M. tuberculosis, L. infantum may use BM-MSCs as an infectious niche
Summary
Visceral leishmaniasis (VL) is caused by Leishmania donovani-complex organisms and is endemic in the tropical and subtropical areas of the World. The parasites change from the promastigote to amastigote form, proliferate, and after lysis of the host cells again infect other target cells [2]. Leishmania parasites reside primarily inside Mononuclear Phagocytic System (MFS) cells [3]. Other cells have been reported to be susceptible to Leishmania infection such as fibroblasts [4], amniotic epithelial cells [5], human epithelial cells [5], hepatocytes [6] and adipose tissue-derived mesenchymal stem cells [7]. Mesenchymal stem cells (MSC) can be derived from a variety of different sources and are characterized as a population of cells with high proliferative capacity, that adhere to plastic, have specific surface antigen expression, and multipotent differentiation potential [8]. The CD271 marker has been proposed as one of the most specific marker for the purification and PLOS ONE | DOI:10.1371/journal.pone.0162927 September 13, 2016
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