Department of Infectious Diseases, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Sino-French Hoffmann Institute, Department of Basic Medical Science, Guangzhou Medical University, Guangzhou, China.
Front Immunol. 2023 Apr 27;14:1123074. doi: 10.3389/fimmu.2023.1123074. eCollection 2023.
Splenomegaly is a prominent clinical manifestation of malaria and the causes remain incompletely clear. Anemia is induced in malaria and extramedullary splenic erythropoiesis is compensation for the loss of erythrocytes. However, the regulation of extramedullary splenic erythropoiesis in malaria is unknown. An inflammatory response could facilitate extramedullary splenic erythropoiesis in the settings of infection and inflammation. Here, when mice were infected with rodent parasites, NSM, TLR7 expression in splenocytes was increased. To explore the roles of TLR7 in splenic erythropoiesis, we infected wild-type and C57BL/6 mice with NSM and found that the development of splenic erythroid progenitor cells was impeded in mice. Contrarily, the treatment of the TLR7 agonist, R848, promoted extramedullary splenic erythropoiesis in wild-type infected mice, which highlights the implication of TLR7 on splenic erythropoiesis. Then, we found that TLR7 promoted the production of IFN-γ that could enhance phagocytosis of infected erythrocytes by RAW264.7. After phagocytosis of infected erythrocytes, the iron metabolism of RAW264.7 was upregulated, evidenced by higher iron content and expression of and . Additionally, the neutralization of IFN-γ impeded the extramedullary splenic erythropoiesis modestly and reduced the iron accumulation in the spleen of infected mice. In conclusion, TLR7 promoted extramedullary splenic erythropoiesis in NSM-infected mice. TLR7 enhanced the production of IFN-γ, and IFN-γ promoted phagocytosis of infected erythrocytes and the iron metabolism of macrophages , which may be related to the regulation of extramedullary splenic erythropoiesis by TLR7.
脾肿大是疟疾的一个突出临床表现，其病因尚不完全清楚。疟疾可导致贫血，脾外造血是对红细胞丢失的代偿。然而，疟疾脾外造血的调节机制尚不清楚。在感染和炎症的情况下，炎症反应可能促进脾外造血。在这里，当小鼠感染啮齿动物寄生虫时，脾细胞中的 NSM 和 TLR7 表达增加。为了探讨 TLR7 在脾造血中的作用，我们用 NSM 感染野生型和 C57BL/6 小鼠，发现 小鼠脾红系祖细胞的发育受到阻碍。相反，TLR7 激动剂 R848 的治疗促进了野生型感染小鼠的脾外造血，这突出了 TLR7 对脾造血的影响。然后，我们发现 TLR7 促进 IFN-γ的产生，IFN-γ可以增强 RAW264.7 吞噬感染红细胞的能力。吞噬感染的红细胞后，RAW264.7 的铁代谢上调，表现为铁含量和 和 的表达增加。此外，IFN-γ 的中和作用适度地阻碍了脾外造血，并减少了感染小鼠脾脏中的铁积累。总之，TLR7 促进了 NSM 感染小鼠的脾外造血。TLR7 增强了 IFN-γ的产生，IFN-γ促进了感染红细胞的吞噬作用和巨噬细胞的铁代谢，这可能与 TLR7 调节脾外造血有关。
