Single-cell RNA sequencing reveals unique alterations in the immune landscape and Treg subpopulations in mice after Echinococcus granulosus infection [TCR BCR]
Cystic echinococcosis (CE) is a common zoonotic parasitic disease that seriously impacts public health. However, the full spectrum of immune cell changes in Echinococcus granulosus (E. granulosus) infection, especially the negative immune regulation of subpopulations of regulatory T cells (Treg), are not yet well understood. In this study, we aimed to identify the panoramic landscape of changes in immune cells and molecules and the distinct alterations in Treg subpopulations in mice infected with E. granulosus. We used single-cell RNA sequencing and single-cell T/B cell receptor sequencing to analyze 53,298 cells from the spleen and peripheral blood mononuclear cells (PBMCs) of healthy and E. granulosus-infected mice. We used immunofluorescence combined with RNA fluorescence in situ hybridization and quantitative real-time polymerase chain reaction to verify the sequencing results. Our results showed organ-specific immune system alterations in mice infected with E. granulosus. E. granulosus-infected mice induced a subpopulation of CD4+ cells with type I interferon production potential. Furthermore, there were seven different Treg cell subpopulations in vivo at three stages of differentiation, and Treg subpopulations of different classes and different stages of differentiation showed tissue specificity. After infection, the Lag3hi Treg and Gpr83+Igfbp4+ naïve Treg subpopulations were specifically induced in PBMCs and spleen, respectively. Furthermore, T follicular helper 2(Tfh2) cells with high expression of Cxxc5 and Spock2 were found in E. granulosus-infected mice. Additionally, combined single-cell immunome repertoire sequencing analysis revealed that gene fragment expression of multiple VJ-paired combinations of T cell receptor ß chains were downregulated after infection. Our data uncovered changes in the full spectrum of immune cells in mice following E. granulosus infection, including subpopulations of cells that have not been emphasized in previous studies. These results further enrich the study of the bidirectional immunomodulatory mechanism and offer a different perspective for subsequent studies of E. granulosus infection. Overall design: Examination of mice spleen and PBMCs cells by single cell sequencing