Differential Analysis of Key Proteins Related to Fibrosis and Inflammation in Soluble Egg Antigen of Schistosoma mansoni at Different Infection Times

Abstract

Schistosomiasis is a major global health problem. Schistosomes secrete antigens into the host tissue that bind to chemokines or inhibit immune cell receptors, regulating the immune responses to allow schistosome development. However, the detailed mechanism of chronic schistosome infection-induced liver fibrosis, including the relationship between secreted soluble egg antigen (SEA) and hepatic stellate cell (HSC) activation, is still unknown. We used mass spectrometry to identify the SEA protein sequences from different infection weeks. In the 10th and 12th infection weeks, we focused on the SEA components and screened out the special protein components, particularly fibrosis- and inflammation-related protein sequences. Our results have identified heat shock proteins, phosphorylation-associated enzymes, or kinases, such as Sm16, GSTA3, GPCRs, EF1-α, MMP7, and other proteins linked to schistosome-induced liver fibrosis. After sorting, we found many special proteins related to fibrosis and inflammation, but studies proving their association with schistosomiasis infection are limited. Follow-up studies on MICOS, MATE1, 14-3-3 epsilon, and CDCP1 are needed. We treated the LX-2 cells with the SEA from the 8th, 10th, and 12th infection weeks to test HSC activation. In a trans-well cell model in which PBMCs and HSCs were co-cultured, the SEA could significantly induce TGF-β secretion, especially from the 12th week of infection. Our data also showed that TGF-β secreted by PBMC after the SEA treatment activates LX-2 and upregulates hepatic fibrotic markers α-SMA and collagen 1. Based on these results, the CUB domain-containing protein 1 (CDCP1) screened at the 12th infection week could be investigated further. This study clarifies the trend of immune mechanism variation in the different stages of schistosome infection. However, how egg-induced immune response transformation causes liver tissue fibrosis needs to be studied further.