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Mycobacterium tuberculosis (MTB) antigen-induced upregulation of interleukin-35 expression in patients with MTB infection: In vitro blockade of the effects of interleukin-35 on T lymphocyte subsets
Pathogens and Disease ( IF 2.7 ) Pub Date : 2021-07-08 , DOI: 10.1093/femspd/ftab035
Hongbin Jiang 1 , Beinian Cui 2 , Jun Zhang 2
Affiliation  

Immunosuppressive interleukin-35 (IL-35) serum concentrations were analyzed in patients with active pulmonary Mycobacterium tuberculosis (MTB) infections (PTB), PTB patients after two months treatment (stable PTB) and healthy controls. IL-35 concentrations were highest in active PTB followed by stable PTB cases and lowest in healthy control participants (all P < 0.01). The same trents were found for supernatants of isolated blood mononuclear cells (PBMCs), with additional enhancements after MTB antigen stimulation only for PBMCs of active and stable PTB patients (P < 0.001), for EBI3 and IL-12a transcriptions in PBMCs (P < 0.001) and percentages of EBI3 expressing (CD4 + CD25 + Foxp3+) regulatory T cells (Treg) (P < 0.001). IL-35 antibody applications significantly reversed MTB antigen stimulated IL-35 and IL-10 expression in PBMCs of active and stable PTB patients, and reduced Foxp3 expression in CD4 + CD25 + cells and EBI3 expression in Treg cells, but had no effects on healthy control cells. The percentages of Th1 and Th17 cells in CD4 + cells were enhanced after MTB antigen stimulation of cells taken from active and stable PTB patients, which were partly increased only for Th1 cells after IL-35 antibody exposure. MTB antigen-driven upregulation of IL-35 may lead to reduced immune surveillance in PTB patients.

中文翻译:

结核分枝杆菌 (MTB) 抗原诱导的 MTB 感染患者 IL-35 表达上调:IL-35 对 T 淋巴细胞亚群影响的体外阻断

在活动性肺结核分枝杆菌 (MTB) 感染 (PTB) 患者、治疗两个月后的 PTB 患者 (稳定的 PTB) 和健康对照组中分析免疫抑制性白细胞介素 35 (IL-35) 的血清浓度。IL-35 浓度在活动性 PTB 中最高,其次是稳定的 PTB 病例,在健康对照参与者中最低(所有 P < 0.01)。对于分离的血液单个核细胞 (PBMC) 的上清液也发现了相同的趋势,MTB 抗原刺激后仅对活跃和稳定的 PTB 患者的 PBMC (P < 0.001),对于 PBMC 中的 EBI3 和 IL-12a 转录有额外的增强 (P < 0.001) 和表达 EBI3 (CD4 + CD25 + Foxp3+) 调节性 T 细胞 (Treg) 的百分比 (P < 0.001)。IL-35 抗体应用显着逆转 MTB 抗原刺激的活动性和稳定 PTB 患者 PBMC 中 IL-35 和 IL-10 的表达,并降低 CD4 + CD25 + 细胞中的 Foxp3 表达和 Treg 细胞中的 EBI3 表达,但对健康无影响控制细胞。对取自活跃和稳定的 PTB 患者的细胞进行 MTB 抗原刺激后,CD4 + 细胞中 Th1 和 Th17 细胞的百分比增加,仅在 IL-35 抗体暴露后 Th1 细胞部分增加。MTB 抗原驱动的 IL-35 上调可能导致 PTB 患者的免疫监视减少。对取自活跃和稳定的 PTB 患者的细胞进行 MTB 抗原刺激后,CD4 + 细胞中 Th1 和 Th17 细胞的百分比增加,仅在 IL-35 抗体暴露后 Th1 细胞部分增加。MTB 抗原驱动的 IL-35 上调可能导致 PTB 患者的免疫监视减少。对取自活跃和稳定的 PTB 患者的细胞进行 MTB 抗原刺激后,CD4 + 细胞中 Th1 和 Th17 细胞的百分比增加,仅在 IL-35 抗体暴露后 Th1 细胞部分增加。MTB 抗原驱动的 IL-35 上调可能导致 PTB 患者的免疫监视减少。
更新日期:2021-07-08
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