A preliminary investigation into the immune cell landscape of schistosome‐associated liver fibrosis in humans

Abstract

Schistosomiasis is a widespread helminth disease that poses a heavy social and economic burden on people worldwide. Advanced schistosomiasis often develops into schistosome-associated liver fibrosis, the pathogenesis of which remains unclear. This study aimed preliminarily to profile immune cells of schistosome-associated liver fibrosis using single-cell RNA sequencing. Three patient groups were enrolled, including an Schistosomiasis japonicum (SJ) group (n = 1), a chronic liver failure (CLF) group (n = 3) and a healthy control (HC) group (n = 2), revealing 17 cell clusters out of 20 093 cells. From these limited datasets, it was observed that T cell-1, mononuclear phagocytes(MP)-1 and dendritic cells (DCs) were higher in the SJ group. CAVIN2 + MP(2) was the predominant cell type in the MP subset of the SJ group (53%), and was higher than that in both the CLF (8%) and HC (1%) groups. Kupffer cell marker genes (CD163, MARCO and TIMD4) were enriched in caveolaeassociated protein 2 (CAVIN2) + MP(2), which was also an important source of TGFB1. The KEGG pathways of CAVIN2 + MP(2) indicated that they were associated with lysosome, endocytosis, phagosome and antigen processing and presentation. The preliminary study showed that granzyme B (GZMB) + T cell (1) and ankyrin repeat domain-containing protein 36B + T cell(3) were the most common T cells in the SJ group (50% and 32%, respectively). The KEGG pathways of GZMB + T cell(1) were mainly related to natural killer cellmediated cytotoxicity. The percentage of ring1 and YY1 binding protein (RYBP) + DC(1) was higher in the SJ group (57%) than in the CLF (16%) and HC (6%) groups. The KEGG pathway of RYBP + DC(1) was related to Fc gamma R-mediated phagocytosis and antigen processing and presentation. Overall, CAVIN2 + Kupffer cells were the main source of TGFB1, consisting primarily of mononuclear phagocytes in the livers of the SJ group subjects and potentially playing an irreplaceable role in hepatic fibrosis of schistosomiasis.

Single-cell RNA sequencing reveals a peripheral landscape of immune cells in Schistosomiasis japonica

“…Our results showed that CXCR2 + NKT cells might migrate to the liver via chemotaxis and exhibit both cytotoxic and proinflammatory activity. Our previous study also showed that GZMB + T cells are increased in schistosome -associated liver fibrosis [ 37 ]. Previous studies have also demonstrated the importance of NKT cells in hepatic inflammation and fibrosis.…”

Single‐cell RNA sequencing reveals the heterogeneity and intercellular communication of hepatic stellate cells and macrophages during liver fibrosis

“…Cell population source analysis and immunofluorescence labeling showed that the mouse fibrosis model contained highly expressing Ccr2 and Cd68 cell populations (Figures 4E, H , and S3B ). Cells in cluster 2 were identified as Kupffer cells (KCs) because of the high expression of KC marker genes Clec4f , Macro and Timd4 42 (Figures 4F and G ). Percent cell population analysis and Clec4f immunofluorescence staining indicated that this cell population was mainly derived from normal mouse liver (Figures 4E and I ).…”

Liver in infections: a single-cell and spatial transcriptomics perspective

“…Advanced schistosomiasis often progresses to liver fibrosis and cirrhosis. To characterise the transcriptomic atlas of liver immune cells involved in schistosoma-associated fibrosis, scRNA-seq analysis was performed on liver samples from fibrotic patients coinfected with S. japonicum (SJ) schistosoma and HBV, patients with HBV cirrhosis, and healthy controls [ 153 ]. Despite the small sample size, this study revealed that T cells, particularly granzyme B (GZMB)+ T cells, were a major subgroup of liver-resident immune cells and increased in the SJ group.…”