Liu Qiannan, Wang Nian, Sun Hengchang, Dong Huimin, Li Xuerong, Yu Xinbing, Huang Yan
Department of Parasitology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, Guangdong, PR China; Department of Nutrition, Jiangmen Central Hospital, Jiangmen 529030, Guangdong Province, PR China; Key Laboratory for Tropical Diseases Control, Ministry of Education, Sun Yat-Sen University, Guangzhou 510080, Guangdong, PR China.
Department of Parasitology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, Guangdong, PR China; Key Laboratory for Tropical Diseases Control, Ministry of Education, Sun Yat-Sen University, Guangzhou 510080, Guangdong, PR China; Provincial Engineering Technology Research Center for Diseases-vectors Control, Guangzhou 510080, Guangdong, PR China.
Acta Trop. 2024 Dec;260:107405. doi: 10.1016/j.actatropica.2024.107405. Epub 2024 Sep 15.
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 CD4IL-4 T cells and IL-4 increased, while CD4INF-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.
华支睾吸虫（C. sinensis）与乙型肝炎病毒（HBV）合并感染在华支睾吸虫病流行地区较为常见。华支睾吸虫或HBV的慢性感染更易发生。然而，与合并感染发病机制相关的免疫机制仍不清楚。在本研究中，为了进一步了解合并感染期间的免疫反应，研究了髓源性抑制细胞（MDSCs）的积累、骨髓来源的树突状细胞（BMDCs）反应以及华支睾吸虫排泄分泌产物（CsESP）和乙型肝炎e抗原（HBeAg）体外共孵育对Th1/Th2极化的后续影响。结果表明，与单独的CsESP或HBeAg相比，共刺激主要促进了MDSCs的积累。共刺激显著下调了BMDCs的CD80和CD86表达，减少了IL-12p70释放，同时增加了IL-10水平。共处理的BMDCs膜受体中检测到甘露糖受体（MR）转录水平较高，而Toll样受体4（TLR-4）的mRNA水平较低。此外，在用CsESP和HBeAg处理的LPS刺激的BMDCs刺激CD4初始T细胞后，CD4IL-4 T细胞和IL-4的比例增加，而CD4INF-γ T细胞百分比和INF-γ下调。总之，CsESP和HBeAg共孵育更明显地抑制了BMDCs的成熟，通过上调BMDCs的MR和下调TLR-4，极有可能导致IL-10增加和IL-12减少，并相继诱导Th2免疫偏移。这些发现为进一步阐明合并感染期间的免疫反应奠定了基础，有助于更好地精确治疗和评估合并感染患者的病情进展。
