ISGlobal, Barcelona Institute for Global Health, Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.
IGTP Institut d'Investigació Germans Trias i Pujol, Ctra. de Can Ruti, Barcelona, Spain.
Front Cell Infect Microbiol. 2024 May 17;14:1408451. doi: 10.3389/fcimb.2024.1408451. eCollection 2024.
Recent studies indicate that human spleen contains over 95% of the total parasite biomass during chronic asymptomatic infections caused by . Previous studies have demonstrated that extracellular vesicles (EVs) secreted from infected reticulocytes facilitate binding to human spleen fibroblasts (hSFs) and identified parasite genes whose expression was dependent on an intact spleen. Here, we characterize the spleen-dependent hypothetical gene (PVX_114580). Using CRISPR/Cas9, PVX_114580 was integrated into 3D7 genome and expressed during asexual stages. Immunofluorescence analysis demonstrated that the protein, which we named (PvSDP1), was located at the surface of infected red blood cells in the transgenic line and this localization was later confirmed in natural infections. Plasma-derived EVs from -infected individuals (PvEVs) significantly increased cytoadherence of 3D7_PvSDP1 transgenic line to hSFs and this binding was inhibited by anti-PvSDP1 antibodies. Single-cell RNAseq of PvEVs-treated hSFs revealed increased expression of adhesion-related genes. These findings demonstrate the importance of parasite spleen-dependent genes and EVs from natural infections in the formation of intrasplenic niches in , a major challenge for malaria elimination.
最近的研究表明，在由 引起的慢性无症状感染期间，人类脾脏中含有超过 95%的寄生虫总生物量。先前的研究表明，从感染的网织红细胞中分泌的细胞外囊泡 (EVs) 有助于与人类脾脏成纤维细胞 (hSFs) 结合，并鉴定出寄生虫基因，其表达依赖于完整的脾脏。在这里，我们描述了依赖脾脏的假设基因 (PVX_114580)。使用 CRISPR/Cas9，将 PVX_114580 整合到 3D7 基因组中，并在无性阶段表达。免疫荧光分析表明，该蛋白，我们命名为 (PvSDP1)，位于转基因系感染的红细胞表面，这一定位在天然感染中得到了证实。来自 - 感染个体的血浆衍生的 EVs (PvEVs) 显著增加了 3D7_PvSDP1 转基因系对 hSFs 的细胞黏附，并且这种结合被抗 PvSDP1 抗体抑制。用 PvEVs 处理的 hSFs 的单细胞 RNAseq 显示出与粘附相关的基因表达增加。这些发现表明寄生虫依赖脾脏的基因和来自天然感染的 EVs 在 中形成脾内龛位的重要性，这是消除疟疾的主要挑战。
