# Plasmodium vivax tryptophan-rich antigen reduces type I collagen secretion via the NF-κBp65 pathway in splenic fibroblasts

## TL;DR

This study shows that certain Plasmodium vivax proteins reduce collagen I in human spleen cells by activating an inflammatory pathway.

## Contribution

The study identifies five new PvTRAg proteins that affect collagen I via the NF-κBp65 pathway in splenic fibroblasts.

## Key findings

- Five PvTRAgs activate the NF-κBp65 pathway in human splenic fibroblasts.
- Activation of this pathway leads to reduced collagen I levels and increased inflammatory molecules.
- Twenty-three PvTRAg proteins were expressed and purified for functional analysis.

## Abstract

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.

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.

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.

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.

The online version contains supplementary material available at 10.1186/s13071-024-06264-y.