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

Abstract

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.

FT-GPI, a highly sensitive and accurate predictor of GPI-anchored proteins, reveals the composition and evolution of the GPI proteome in Plasmodium species

“…For those proteins predicted not to be GPI-APs (GPI-AP-) by TMPred, the SignalP 5.0 score was also less than 0.7 (Additional file 4: Table S4), but some GPI-APs such as MSPs had very low score, highlighting the difficulty of SignalP in identifying candidates in P. falciparum in general. The TMPred negative prediction of well characterized surface-related antigen (SRA) orthologs [56,57] was intriguing. In fact, SRA proteins had a TM downstream of the SP putative cleavage site.…”

Plasmodium yoelii surface-related antigen (PySRA) modulates the host pro-inflammatory responses via binding to CD68 on macrophage membrane

“…The SRA protein is regarded as a potential candidate antigen for the malaria vaccine because the N-terminal of PfSRA is highly conserved by gene polymorphism analysis ( 22 ). In addition, PvSRA could interact with Integrin β1 (ITGB1) on the surface of human splenic fibroblasts (HSFs), participating in the regulation of immune responses ( 23 ). However, the functional properties of SRA cannot be verified in vivo due to moral and ethical constraints.…”