Single-Cell RNA Sequencing Reveals the Heterogeneity of Infiltrating Immune Cell Profiles in the Hepatic Cystic Echinococcosis Microenvironment

Abstract

Human cystic echinococcosis, caused by the larval stage of echinococcus granulus sensu lato , has been reported a near-cosmopolitan zoonotic disease. Various infiltrating immune cells gather around the lesion and produce lesion microenvironment, however cellular composition and heterogeneity in hepatic cystic echinococcosis lesion microenvironment are incompletely understood. Here, 81,865 immune cells isolated from peripheral blood, peri-lesion liver tissue, and adjacent normal liver tissue from four cystic echinococcosis patients were profiled using single-cell RNA sequencing. We identified 23 discrete cell populations, and found distinct differences in infiltrating immune cells between tissue environments. Despite the significant similarity between peri-lesion and adjacent normal liver tissue-resident immune cells, the cellular proportions of innate lymphocyte 2 and plasmacytoid dendritic cells were higher in peri-lesion liver tissue. Interestingly, the immunosuppressive gene NFKBIA was up-regulated in these cells. Seven subsets of CD4 + T cell populations were found, and there were more Treg-CD4 + T and Th2-CD4 + T cells in peri-lesion tissue than those in adjacent normal tissue. There was close contact between CD4 + T cells and ILC2 and pDCs cells, which caused up-regulation of genes related to positive immune activity in adjacent normal liver tissue. However, expression of genes related to immunosuppression, especially the immune inhibitory checkpoint gene NKG2A/HLA-E, was obviously higher in peri-lesion tissue, suggesting that cellular interaction resulted in an inhibitory microenvironment in the CE lesion. This work offers new insights into the transcriptional heterogeneity of infiltrating immune cells in hepatic cystic echinococcosis lesion microenvironment at single-cell level, and provides potential target signatures for diagnosis and immunotherapies.

Single-cell sequencing of PBMC characterizes the altered transcriptomic landscape of classical monocytes in BNT162b2-induced myocarditis

“…After annotating each cluster, we calculated the proportion of cells originating at each time point for each cell cluster ( Figure 2A ). The presence of each cluster at every time point implies that the data are well-integrated and highly reproducible ( 21 ). However, there were differences in terms of cell proportions; the cell number across all clusters at the time of myocarditis was similar to that in the early recovery state but different from that in the late recovery state.…”

Spatiotemporal transcriptomic profiling reveals the dynamic immunological landscape of alveolar echinococcosis

“…However, the exact cell composition in the infection tissues and the cellular structural dynamics during sustained infection remain obscure. In the late infection stage, the upregulation of exhaustion-related genes such as NFKBIA, PD-1, CTLA4, TIGIT, and TIM-3 transforms the immune cells including CD4 + and CD8 + T cells into an immune inhibition phenotype, facilitating the persistent propagation of the metacestodes in the host [18][19][20] . Neutrophils are the first leukocytes recruited to eliminate invading pathogens through multiple mechanisms such as NETosis and phagocytosis 21 .…”

“…However, a high-resolution spatial landscape of the infection foci and the cell-cell interaction mechanism driving disease progression remain to be elucidated. To solve this problem, single-cell RNA sequencing (scRNA-seq) can be applied to acquire the transcriptomes of single cells after tissue dissociation, which can reveal the changes in cell types and cell states during parasite infection 18,19 . Meanwhile, the spatial transcriptomics (ST) technology can reveal the cell-cell interactions in specific pathological niches by capturing tissue transcriptomes in situ .…”

Implications of NKG2A in immunity and immune-mediated diseases

“…Human cystic echinococcosis is caused by the larval stage of Echinococcus granulosus sensu lato . The expression of NKG2A and HLA-E was significantly increased within the hepatic cystic echinococcosis lesion, suggesting an inhibitory microenvironment ( 117 ). High expression of NKG2A was observed in human malaria-responsive NK cells ( 118 ) and γδ-T cells ( 119 ), which provided a homeostatic regulation mechanism for avoiding persistent activation.…”