Wellcome Centre for Integrative Parasitology, University of Glasgow, Glasgow, UK.
Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, UK.
Sci Adv. 2022 Apr 29;8(17):eabm7348. doi: 10.1126/sciadv.abm7348. Epub 2022 Apr 27.
Malaria remains a global health problem causing more than 400,000 deaths annually. parasites, the causative agents of malaria, replicate asexually in red blood cells (RBCs) of their vertebrate host, while a subset differentiates into sexual stages (gametocytes) for mosquito transmission. Parasite replication and gametocyte maturation in the erythropoietic niches of the bone marrow and spleen contribute to pathogenesis and drive transmission, but the mechanisms underlying this organ enrichment remain unknown. Here, we performed a comprehensive analysis of rodent infection by flow cytometry and single-cell RNA sequencing. We identified CD71 as a host receptor for reticulocyte invasion and found that parasites metabolically adapt to the host cell environment. Transcriptional analysis and functional assays further revealed a nutrient-dependent tropism for gametocyte formation in reticulocytes. Together, we provide a thorough characterization of host-parasite interactions in erythropoietic niches and define host cell maturation state as the key driver of parasite adaptation.
疟疾仍然是一个全球性的健康问题，每年导致超过 40 万人死亡。疟原虫是疟疾的病原体，在脊椎动物宿主的红细胞（RBC）中进行无性繁殖，而一部分则分化为有性阶段（配子体）以进行蚊子传播。寄生虫在骨髓和脾脏的造血龛位中的复制和配子体成熟有助于发病机制和传播，但这种器官富集的机制尚不清楚。在这里，我们通过流式细胞术和单细胞 RNA 测序对啮齿动物感染进行了全面分析。我们确定 CD71 是网织红细胞入侵的宿主受体，并发现寄生虫在代谢上适应了宿主细胞环境。转录分析和功能测定进一步显示，配子体形成对网织红细胞有营养依赖性的趋向性。总之，我们对红细胞生成龛位中的宿主-寄生虫相互作用进行了全面描述，并将宿主细胞成熟状态定义为寄生虫适应的关键驱动因素。
