Malaria remains a major public health problem worldwide. The immune mechanisms that mediate protection against malaria are still unclear. Previously, we reported that mesenchymal stem cells (MSCs) play a critical role in host protection against malaria by altering the dynamic balance of T regulatory cells and effector T cells producing inflammatory cytokines. Here, we report that MSCs reprogram haematopoiesis in primary (bone marrow) and secondary (spleen) lymphoid organs to provide host protection against malaria. Adoptive transfer of MSCs from malaria-infected mice to naïve recipient mice that were subsequently infected with malaria parasites dramatically accelerated the formation of colony-forming units-erythroid cells in the bone marrow. Adoptively transferred MSCs also induced expression of the key erythroid cell differentiation factor GATA-1 in the spleen of recipient animals. Interestingly, we further observed a subtle increase in the CD34⁺ hematopoietic stem and progenitor cells in lymphoid organs, including spleen and lymph nodes. Infusion of MSCs also enhanced T cell proliferation, resulting in increased numbers of both CD4⁺ and CD8⁺ T cells in the spleen. MSCs also inhibited the induction of the negative co-stimulatory receptor programmed death-1 by T cells in recipient animals upon infection with malaria parasites. Taken together, our findings suggest that MSCs play a critical role in host protection against malaria infection by modulating erythropoiesis and lymphopoiesis.

疟疾仍然是世界范围内的主要公共卫生问题。尚不清楚介导针对疟疾的保护的免疫机制。以前，我们报道了间充质干细胞（MSC）通过改变T调节细胞和产生炎症细胞因子的效应T细胞的动态平衡，在宿主对抗疟疾的保护中起着至关重要的作用。在这里，我们报告说，MSC重新编程了原发性（骨髓）和继发性（脾脏）淋巴器官中的造血功能，以提供针对疟疾的宿主保护。MSCs从疟疾感染小鼠过继转移到幼稚的受体小鼠中，随后这些小鼠随后感染了疟原虫，从而极大地促进了骨髓中集落形成单位红系细胞的形成。过继转移的MSC还诱导受体动物脾脏中关键类红细胞分化因子GATA-1的表达。有趣的是，我们进一步观察到CD34的微妙增加⁺淋巴器官（包括脾脏和淋巴结）中的造血干细胞和祖细胞。输注MSCs还增强了T细胞增殖，导致脾脏中CD4 ⁺和CD8 ⁺ T细胞的数量增加。在感染疟疾寄生虫后，MSC还抑制了受体细胞中T细胞对负共刺激受体程序性死亡1的诱导。综上所述，我们的发现表明，MSC通过调节红细胞生成和淋巴细胞生成，在宿主抵抗疟疾感染的保护中起着关键作用。