scRNA + TCR + BCR-seq Reveals the proportion and characteristics of dual TCR T cells and dual BCR B cells in mice infected with Echinococcus granulosus

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Abstract

Cystic echinococcosis (CE) is a zoonotic parasitic disease caused by Echinococcus granulosus, and the T and B cell responses and regulatory mechanisms in CE remain unclear. In this study, we analyzed the data of peripheral blood and spleen of mice infected with Echinococcus granulosus(EG) by scRNA+TCR+BCR-seq, and made the following novel findings: (1) Peripheral blood of Echinococcus granulosus (EG)-infected mice contained a higher proportion of dual TCR(T cell receptor) T cells with higher clonality than uninfected mice; (2) There was a bias in V gene usage between single TCR T and dual TCR T cells, as well as between single BCR(B cell receptor) B cells and dual BCR B cells in EG-infected mice; (3) Dual TCR Tregs, dual TCR effector CD8 T cells, dual BCR Bregs, and dual BCR memory/dividing B cells exhibited relatively high clonal expansion in EG-infected mice; (4) Shared CDR3 sequences and consistently highly expressed mRNA molecules exist between single receptor T/B and dual receptor T/B cells in EG-infected mice. KEGG enrichment analysis revealed that dual BCR B cells are closely related to the expression of factors associated with pathways such as “Th1/Th2 differentiation” and “antigen processing and presentation”. These results suggest that dual TCR T and dual BCR B cells may be involved in the specific responses and regulation of EG-infected mice, providing a novel perspective for the adaptive immune response mechanisms and targeted therapy of parasitic infections.

Author summary

Echinococcosis is a zoonotic disease currently prevalent mainly in various parts of Africa. At present, it cannot be completely cured; treatment relies solely on medication to alleviate symptoms. The immunoregulatory mechanisms underlying the disease remain unclear. Using single-cell RNA sequencing, we have identified a novel T- and B-cell subpopulation that may play a role in the immune response to the parasite. This finding opens a new avenue for researchers investigating parasitic diseases.

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