Table2_Identification of the Recombinant Plasmodium vivax Surface-Related Antigen as a Possible Immune Evasion Factor Against Human Splenic Fibroblasts by Targeting ITGB1.XLSX

Plasmodium vivax–infected erythrocytes can enter the spleen and evade spleen clearance to establish chronic infections. However, the mechanism underlying P. vivax immune evasion in the spleen is still unclear. Human splenic fibroblasts (HSF), also known as barrier cells, play an essential role in the immune function of spleen. A hypothesis holds that P. vivax—infected erythrocytes induce spleen structural remodeling to form barrier cells. Subsequently, these infected erythrocytes can selectively cytoadhere to these barrier cells to escape spleen clearance. In this work, we found that P. vivax surface-related antigen (PvSRA; PlasmoDB ID: PVX_084970), an exported protein on infected erythrocyte membrane, could bind with HSF. Considering the above hypothesis, we speculated that PvSRA might be involved in P. vivax immune evasion by changing HSF cell performance. To investigate this speculation, RNA sequencing, protein microarray, and bioinformatics analysis technologies were applied, and in vitro validations were further performed. The results showed that the recombinant PvSRA attracted HSF migration and interacted with HSF by targeting integrin β1 (ITGB1) along with changes in HSF cell performance, such as focal adhesion, extracellular matrix, actin cytoskeleton, and cell cycle. This study indicated that PvSRA might indeed participate in the immune evasion of P. vivax in the spleen by changing HSF function through PvSRA–ITGB1 axis.

间日疟原虫（Plasmodium vivax）感染的红细胞可侵入脾脏并逃避脾脏清除，从而建立慢性感染。然而，间日疟原虫在脾脏内的免疫逃逸机制仍不明确。人类脾脏成纤维细胞（Human splenic fibroblasts, HSF），又称屏障细胞，在脾脏免疫功能中发挥关键作用。有假说提出，间日疟原虫感染的红细胞可诱导脾脏结构重塑，形成屏障细胞；随后这些感染的红细胞可选择性黏附于这些屏障细胞，以逃避脾脏清除。本研究发现，间日疟原虫表面相关抗原（PvSRA; PlasmoDB数据库编号：PVX_084970）作为感染红细胞膜上的导出蛋白，可与HSF结合。结合上述假说，我们推测PvSRA可能通过改变HSF的细胞功能参与间日疟原虫的免疫逃逸过程。为验证这一推测，本研究采用了RNA测序、蛋白质芯片及生物信息学分析技术，并进一步开展了体外验证实验。结果显示，重组PvSRA可趋化HSF迁移，并通过靶向整合素β1（integrin β1, ITGB1）与HSF发生相互作用，同时可改变HSF的细胞功能，包括黏着斑、细胞外基质、肌动蛋白细胞骨架及细胞周期相关通路的变化。本研究表明，PvSRA可能确实通过PvSRA-ITGB1轴改变HSF功能，从而参与间日疟原虫在脾脏内的免疫逃逸过程。