He Jinlei, Huang Fan, Liao Xuechun, Zhang Jianhui, Wei Shulan, Xiao Yuying, Zheng Xiaoting, Zhu Zheying, Chen Dali, Chen Jianping
Department of Pathogenic Biology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China.
First Surgical Department, Chengdu Shuangliu Hospital of Traditional Chinese Medicine, Chengdu, China.
Acta Trop. 2023 Jun;242:106921. doi: 10.1016/j.actatropica.2023.106921. Epub 2023 Apr 6.
As important immunomodulators, CpG ODNs have broad application prospects in the treatment and prevention of leishmaniasis. In order to explore the immunomodulatory effect of CpG ODNs on mice infected with Leishmania parasites in different nutritional status, TLR9 agonist CpG ODN 2395 or TLR9 antagonist CpG ODN 2088 was injected into normal, obesity and undernutrition BALB/c mice infected with Leishmania donovani, respectively. Subsequently, spleen and liver parasite loads, spleen and liver immune gene expression, spleen T cell subsets proportion and PD-1 expression, serum lipids, serum cytokines, and anti-Leishmania antibodies were measured to assess the immune response of mice with different nutritional status. The results displayed that at the 8th week after infection, the spleen parasite load of obesity and undernutrition mice was significantly higher than that of normal mice, but the liver parasite load showed no statistical difference among the three groups. The treatment of CpG ODN 2395 or CpG ODN 2088 significantly reduced the spleen parasite load of obesity and undernutrition infected mice, but did not reduce that of normal infected mice. In obesity infected mice, CpG ODN 2395 promoted the up-regulation of TCR, ICOS and TLR4 in spleen, promoted the secretion of IFN-γ and anti-Leishmania total IgG and IgG1 antibodies, and increased the content of serum HDL-C. In undernutrition infected mice, CpG ODN 2395 promoted the up-regulation of spleen CD28 and TLR9, increased the proportion of spleen CD3 T cells, and decreased the content of serum IL-10. Our results demonstrated that CpG ODN 2395 enhanced the immune response and clearance of Leishmania parasites in obesity and undernutrition mice, which might be used as a therapeutic agent for obesity and undernutrition leishmaniasis patients in the future.
作为重要的免疫调节剂，CpG寡脱氧核苷酸在利什曼病的治疗和预防中具有广阔的应用前景。为了探究CpG寡脱氧核苷酸对处于不同营养状态下感染利什曼原虫的小鼠的免疫调节作用，将TLR9激动剂CpG ODN 2395或TLR9拮抗剂CpG ODN 2088分别注射到感染杜氏利什曼原虫的正常、肥胖和营养不良的BALB/c小鼠体内。随后，检测脾脏和肝脏中的寄生虫载量、脾脏和肝脏免疫基因表达、脾脏T细胞亚群比例和PD-1表达、血脂、血清细胞因子以及抗利什曼原虫抗体，以评估不同营养状态小鼠的免疫反应。结果显示，感染后第8周，肥胖和营养不良小鼠的脾脏寄生虫载量显著高于正常小鼠，但三组小鼠的肝脏寄生虫载量无统计学差异。CpG ODN 2395或CpG ODN 2088处理显著降低了肥胖和营养不良感染小鼠的脾脏寄生虫载量，但未降低正常感染小鼠的脾脏寄生虫载量。在肥胖感染小鼠中，CpG ODN 2395促进脾脏中TCR、ICOS和TLR4的上调，促进IFN-γ以及抗利什曼原虫总IgG和IgG1抗体的分泌，并增加血清HDL-C含量。在营养不良感染小鼠中，CpG ODN 2395促进脾脏CD28和TLR9的上调，增加脾脏CD3 T细胞比例，并降低血清IL-10含量。我们的结果表明，CpG ODN 2395增强了肥胖和营养不良小鼠对利什曼原虫的免疫反应和清除能力，未来可能用作肥胖和营养不良利什曼病患者的治疗药物。
