Tim-3/Galectin-9 pathway and expression of CD8 + Treg cells and related factors in patients with alveolar echinococcosis

Abstract Objective: Host immune status plays a crucial role in the parasitism, lesion activity and disease progression of Echinococcus multilocularis (EM). Therefore, by demonstrating that the Tim-3/galactose lectin-9 signaling pathway has an immunosuppressive function and the expression of CD8 + Treg cells and related factors in patients with alveolar encephalopathy (AE), this study can determine the relationship and function of the Tim-3/galactose lectin-9 understanding signaling pathway with CD8 + Treg cells in AE. Methods: The proportions of CD8 + Treg cells, CD8 + CD28 + IL-10 + T cells, CD8 + CD28 + TGF-β + T cells and Tim-3 + CD8 + Treg cells in peripheral blood were first determined in control subjects (n=30), and AE patients (n=33) were examined by flow cytometry. Foxp3 and Tim-3 / Galectin-9 mRNA levels in peripheral blood PBMC from control and AE patients were then measured by QRT-PCR. Finally, the expression of IL-10, TGF-β and Tim-3 / Galectin-9 in the infected livers of AE patients was verified by immunohistochemistry.Results: 1. The proportions of peripheral blood CD8 + Treg cells (P<0.001), CD8 + CD28 + IL-10 + T cells (P<0.001) and CD8 + CD28 + TGF-β + T cells (P<0.001) were significantly higher in AE patients than in controls. 2. The expression of Tim-3 was significantly upregulated in peripheral blood CD8 + Treg cells in AE patients (P <0.001). 3. Foxp3 (P<0.001) and Tim-3/galactose lectin-9 (P<0.001, P<0.001)) mRNA levels were significantly elevated in peripheral blood PBMC from AE patients, and Foxp3 and Tim-3 (r 2 =0.489, P<0.001) with galactose lectin-9 (r 2 =0.366, P=0.047) mRNA levels were positively correlated. 4. Infected individuals showed higher expression of IL-10 (P<0.001), TGF-β (P<0.001) and Tim-3/galactose lectin-9 (P<0.001, P<0.001) in the livers of AE patients than in the distal part of the infection, with IL-10 expression (r 2 =0.852, P<0.001; r2=0.803 P<0.001) 、TGF-β (r 2 =0.770 P<0.001 ;r 2 =0.806, P<0.001) was positively correlated with Tim-3/galactose lectin-9. Conclusion: This study hypothesized that high expression of Tim-3 on the surface of CD8 + Treg cells in AE patients increases the number and function of CD8 + Treg cells and that expression of the Tim-3/galactose lectin-9 pathway promotes the expression of the transcription factor Foxp3 and the inhibitory cytokines IL-10 and TGF-β. This phenomenon is not conducive to the elimination of multifocal echinococcosis in patients, which ultimately leads to persistent exacerbation of the infection.