Plasmodium vivax Protein PvTRAg23 Triggers Spleen Fibroblasts for Inflammatory Profile and Reduces Type I Collagen Secretion via NF-κBp65 Pathway

Abstract

Plasmodium vivaxis the most widespread human malaria parasite. The spleen is one of the most significant immune organs in the course ofPlasmodiuminfection, and it contains splenic fibroblasts (SFs), which supports immunologic function by secreting type I collagen (collagen I).Plasmodiumproteins have rarely been found to be involved in collagen alterations in the spleen during infection. Here, we selected the proteinP. vivaxtryptophan-rich antigen 23 (PvTRAg23), which is expressed by the spleen-dependent genePv-fam-aand is a member of the PvTRAgs family of export proteins, suggesting that it might have an effect on SFs. The protein specifically reduced the level of collagen I in human splenic fibroblasts (HSFs) and bound to cells with vimentin as receptors. However, such collagen changes were not mediated by binding to vimentin, but rather activating the NF-κBp65 pathway to produce inflammatory cytokines. Collagen impaired synthesis accompanied by extracellular matrix-related changes occurred in the spleen of mice infected withP. yoelii17XNL. Overall, this study is the first one to report and verify the role ofPlasmodiumproteins on collagen in HSFin vitro. Results will contribute to further understanding of host spleen structural changes and immune responses afterPlasmodiuminfection.