Up-regulation of MDSCs accumulation and Th2 biased response to co-stimulation of CsESP from Clonorchis sinensis and HBeAg in vitro.

Publisher: Elsevier Country of Publication: Netherlands NLM ID: 0370374 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-6254 (Electronic) Linking ISSN: 0001706X NLM ISO Abbreviation: Acta Trop Subsets: MEDLINE

Publication: Amsterdam : Elsevier
Original Publication: Basel.

Clonorchis sinensis*/immunology ; Hepatitis B e Antigens*/immunology ; Hepatitis B e Antigens*/metabolism ; Th2 Cells*/immunology ; Myeloid-Derived Suppressor Cells*/immunology ; Dendritic Cells*/immunology ; Toll-Like Receptor 4*/metabolism ; Toll-Like Receptor 4*/genetics; Animals ; Clonorchiasis/immunology ; Clonorchiasis/parasitology ; Up-Regulation ; Receptors, Cell Surface/genetics ; Receptors, Cell Surface/metabolism ; Lectins, C-Type/metabolism ; Lectins, C-Type/genetics ; Mannose Receptor ; Mice ; Mannose-Binding Lectins/metabolism ; Coinfection/immunology ; Coinfection/parasitology ; Coinfection/virology ; Interleukin-10/metabolism ; Interleukin-10/genetics ; Interleukin-10/immunology ; Th1 Cells/immunology ; B7-1 Antigen/metabolism ; B7-1 Antigen/genetics ; Mice, Inbred BALB C ; Female ; Male ; B7-2 Antigen/metabolism ; Interleukin-12/metabolism ; Helminth Proteins/immunology ; Helminth Proteins/pharmacology ; Antigens, Helminth/immunology

Co-infection with Clonorchis sinensis (C. sinensis) and Hepatitis B virus (HBV) are commonly observed in endemic areas of Clonorchiasis. Chronic infection of C. sinensis or HBV is more likely to happen. However, the immune mechanisms related to the pathogenesis of co-infection remain unknown. In the present study, Myeloid-derived suppressor cells (MDSCs) accumulation, bone marrow derived dendritic cells (BMDCs) reaction and the consequent effectors on Th1/Th2 polarization to co-incubation of excretory-secretory products from C. sinensis (CsESP) and Hepatitis B e antigen (HBeAg) in vitro were investigated for further understanding the immune response during co-infection. The results indicated that compared with CsESP or HBeAg alone, co-stimulation dominantly promoted MDSCs accumulation. Co-stimulation significantly downregulated the expression of CD80 and CD86, and reduced IL-12p70 release while augmented IL-10 levels of BMDCs. Higher transcription levels of mannose receptor (MR) while lower mRNA level of toll like receptor 4 (TLR-4) were detected among membrane receptors of BMDCs with co-treatment. In addition, after CD4 naïve T cells were stimulated by LPS-treated BMDCs with CsESP and HBeAg, the proportion of CD4 ⁺ IL-4 ⁺ T cells and IL-4 increased, while CD4 ⁺ INF-γ ⁺ T cells percentage and INF-γ down-regulated. In conclusion, CsESP and HBeAg co-incubation more distinctly suppressed maturation of BMDCs resulting in increase of IL-10 and decrease of IL-12 highly possible by up-regulation of MR and down-regulation of TLR-4 of BMDCs, and successively induce Th2 immune skewing. These findings laid the cornerstone to further clarify immune responses during the co-infection contributing to the better precise treatment and progression assessment of co-infection patients.
Competing Interests: Declaration of competing interest All authors disclosed no relevant relationships.
(Copyright © 2024. Published by Elsevier B.V.)

Keywords: Clonorchis sinensis; Hepatitis B virus e antigen; Th2 immune response; dendritic cells; myeloid-derived suppressor cells

0 (Hepatitis B e Antigens)
0 (Toll-Like Receptor 4)
0 (Receptors, Cell Surface)
0 (Lectins, C-Type)
0 (Mannose Receptor)
0 (Mannose-Binding Lectins)
130068-27-8 (Interleukin-10)
0 (B7-1 Antigen)
0 (B7-2 Antigen)
187348-17-0 (Interleukin-12)
0 (Helminth Proteins)
0 (Antigens, Helminth)

Date Created: 20240917 Date Completed: 20241212 Latest Revision: 20241212

20241213

10.1016/j.actatropica.2024.107405

39288888