Department of Immunology and Molecular Biology, University of Gondar, Gondar, Ethiopia.
Department of Infectious Diseases, Kalmar County Hospital and Linköping University Hospital, Linköping University, Sweden; Division of Infectious Diseases. Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
Tuberculosis (Edinb). 2021 Dec;131:102126. doi: 10.1016/j.tube.2021.102126. Epub 2021 Sep 14.
Helminth induced expansion of regulatory T cells (Tregs) may take part in suppressing protective host responses during tuberculosis (TB), although Tregs functionality and link to TB disease severity remains unexplored. We investigated the species-specific effect of helminths on frequency and TGF-β producing capacity of Tregs, and possible connection to TB disease severity. 89 pulmonary TB patients (PTB) and 69 community controls (CCs) from Gondar, Ethiopia, were included. Clinical disease severity was graded by TB score, and flow cytometry used to characterize Treg frequency and functionality measured as their TGF-β-producing capacity. In helminth positive PTB patients (Helminth+PTB+) compared to helminth negative PTB or CCs, TGF-β Tregs were significantly increased mainly in hookworm coinfection whereas S. mansoni increased TGF-β Tregs in CCs. Treatment of TB and helminths decreased TGF-β Tregs in Helminth+PTB+ at 2 months follow-up. There were no overall differences in the frequency of Tregs in CCs or PTB unless stratification on TB disease severity was performed. At inclusion Helminth+PTB+ had increased frequency of Tregs already at low disease severity, and TGF-β Tregs correlated to intermediate-to-high disease severity. In conclusion, helminth specific increase of TGF-β Tregs in PTB patients was correlated to TB disease severity and was restored following anti-helminth treatment.
寄生虫诱导的调节性 T 细胞（Tregs）扩增可能参与抑制结核病（TB）中的保护性宿主反应，尽管 Tregs 的功能及其与 TB 疾病严重程度的联系仍未得到探索。我们研究了寄生虫对 Tregs 频率和 TGF-β产生能力的种特异性影响，以及与 TB 疾病严重程度的可能联系。我们在埃塞俄比亚贡德尔纳入了 89 例肺结核患者（PTB）和 69 例社区对照者（CC）。通过结核病评分来评估临床疾病严重程度，并通过流式细胞术来评估 Treg 频率和功能，即 TGF-β 产生能力。与寄生虫阴性 PTB 或 CC 相比，寄生虫阳性 PTB 患者（Helminth+PTB+）中，TGF-β Tregs 明显增加，主要是在钩虫合并感染时，而 S. mansoni 在 CC 中增加了 TGF-β Tregs。在 2 个月的随访中，治疗 TB 和寄生虫会减少 Helminth+PTB+中的 TGF-β Tregs。除非对 TB 疾病严重程度进行分层，否则在 CC 或 PTB 中，Tregs 的频率没有总体差异。在纳入时，Helminth+PTB+在疾病严重程度较低时已经具有较高频率的 Tregs，并且 TGF-β Tregs 与中高度疾病严重程度相关。总之，PTB 患者中寄生虫特异性增加的 TGF-β Tregs 与 TB 疾病严重程度相关，并在抗寄生虫治疗后得到恢复。
