RESUMO
BACKGROUND: The spleen plays a critical role in the immune response against malaria parasite infection, where splenic fibroblasts (SFs) are abundantly present and contribute to immune function by secreting type I collagen (collagen I). The protein family is characterized by Plasmodium vivax tryptophan-rich antigens (PvTRAgs), comprising 40 members. PvTRAg23 has been reported to bind to human SFs (HSFs) and affect collagen I levels. Given the role of type I collagen in splenic immune function, it is important to investigate the functions of the other members within the PvTRAg protein family. METHODS: Protein structural prediction was conducted utilizing bioinformatics analysis tools and software. A total of 23 PvTRAgs were successfully expressed and purified using an Escherichia coli prokaryotic expression system, and the purified proteins were used for co-culture with HSFs. The collagen I levels and collagen-related signaling pathway protein levels were detected by immunoblotting, and the relative expression levels of inflammatory factors were determined by quantitative real-time PCR. RESULTS: In silico analysis showed that P. vivax has 40 genes encoding the TRAg family. The C-terminal region of all PvTRAgs is characterized by the presence of a domain rich in tryptophan residues. A total of 23 recombinant PvTRAgs were successfully expressed and purified. Only five PvTRAgs (PvTRAg5, PvTRAg16, PvTRAg23, PvTRAg30, and PvTRAg32) mediated the activation of the NF-κBp65 signaling pathway, which resulted in the production of inflammatory molecules and ultimately a significant reduction in collagen I levels in HSFs. CONCLUSIONS: Our research contributes to the expansion of knowledge regarding the functional role of PvTRAgs, while it also enhances our understanding of the immune evasion mechanisms utilized by parasites.
Assuntos
Antígenos de Protozoários , Colágeno Tipo I , Fibroblastos , Plasmodium vivax , Transdução de Sinais , Baço , Plasmodium vivax/genética , Plasmodium vivax/imunologia , Fibroblastos/parasitologia , Antígenos de Protozoários/genética , Antígenos de Protozoários/imunologia , Antígenos de Protozoários/metabolismo , Animais , Colágeno Tipo I/metabolismo , Colágeno Tipo I/genética , Baço/imunologia , Baço/parasitologia , Fator de Transcrição RelA/metabolismo , Fator de Transcrição RelA/genética , Camundongos , Humanos , Malária Vivax/parasitologia , Malária Vivax/imunologia , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/imunologia , Triptofano/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Biologia ComputacionalRESUMO
Malaria, one of the major infectious diseases in the world, is caused by the Plasmodium parasite. Plasmodium antigens could modulate the inflammatory response by binding to macrophage membrane receptors. As an export protein on the infected erythrocyte membrane, Plasmodium surface-related antigen (SRA) participates in the erythrocyte invasion and regulates the immune response of the host. This study found that the F2 segment of P. yoelii SRA activated downstream MAPK and NF-κB signaling pathways by binding to CD68 on the surface of the macrophage membrane and regulating the inflammatory response. The anti-PySRA-F2 antibody can protect mice against P. yoelii, and the pro-inflammatory responses such as IL-1ß, TNF-α, and IL-6 after infection with P. yoelii are attenuated. These findings will be helpful for understanding the involvement of the pathogenic mechanism of malaria with the exported protein SRA.
