Single-cell transcriptome sequencing reveals immunological mechanisms by which recombinant Echinococcus granulosus P29 protein alleviates airway inflammation in mice with allergic asthma.

Abstract

BACKGROUND: Allergic asthma is a major health burden. The "hygiene hypothesis" links parasitic infections to the prevention and treatment of allergic asthma. Recombinant Echinococcus granulosus P29 protein (rEg.P29) has been shown to induce the conversion of CD4 T cells to Th1 in mice, and is widely sourced for translational applications given its composition and biological safety compared with using fine-grained Echinococcus granulosus or antigenic extracts of cystic fluid. However, its effects on allergic asthma remain unclear. Therefore, in this study, we used experiments to investigate how rEg.P29 relieves airway inflammation in mice with allergic asthma and understand the underlying immune mechanisms. METHODS: Lung histiocytes from mice were examined using single-cell transcriptome sequencing in combination with experimental methods, such as flow cytometry. Serum levels of total immunoglobulin E (IgE), ovalbumin (OVA)-IgE, and inflammatory factors were measured using enzyme-linked immunosorbent assays and cytometric bead array. Finally, cellular communication analysis of target immune cells was performed using bioinformatics approaches. RESULTS: rEg.P29 significantly alleviated OVA-induced histopathological changes in the lungs of mice with allergic asthma; downregulated serum IgE levels; reduced lung tissue eosinophils, Th2, and Th17 cells; and increased Th1 and Treg cells in mouse lung tissues. The possibility of an interconversion between proliferative pathogenic Th2 cells and stem cell-like Th2 cells was noted. In Treg cells, Nr4a1 targets were detected, and a Lag3Tnfrsf9Treg cell population was identified, which may play an important immunosuppressive role. Finally, CellChat analysis showed significant interactions between stem cell-like Th2 and Th1 cells, proliferative pathogenic Th2 and stem cell-like Th2 cells, and Treg and Th1 cells. CONCLUSIONS: rEg.P29 can effectively alleviate OVA-induced airway inflammation in mice with allergic asthma, and multiple T cell subpopulations in lung tissues are collectively involved in the immunological effects of rEg.P29.