Lopes Carolina S, Daifalla Nada, Das Bikul, Dias da Silva Valdo, Campos-Neto Antonio
The Forsyth Institute, Cambridge Massachusetts, United States of America.
Department of Biochemistry, Pharmacology, Physiology and Molecular Biology, Institute for Biological and Natural Sciences, Triângulo Mineiro Federal University, Uberaba, MG, Brazil.
PLoS One. 2016 Sep 13;11(9):e0162927. doi: 10.1371/journal.pone.0162927. eCollection 2016.
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.
内脏利什曼病(VL)是一种严重的致命疾病。治疗药物有毒且无法杀菌。病原体婴儿利什曼原虫和杜氏利什曼原虫可导致活动性和无症状疾病。虽然存在治疗VL的有效药物,但不幸的是,治疗后复发很常见。对于药物为何无法杀菌或这些细胞内病原体如何逃避治疗,人们知之甚少。在此,我们利用VL小鼠模型发现,CD271+/Sca1+骨髓间充质干细胞(BM-MSCs)在体外和体内都很容易被婴儿利什曼原虫感染。由于BM-MSCs表达强效药物外排泵,例如ABCG2,这种独特的细胞内感染生态位有可能使婴儿利什曼原虫逃避抗寄生虫药物。