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Differential effects of asymptomatic Ascaris lumbricoides, Schistosoma mansoni or hook worm infection on the frequency and TGF-beta-producing capacity of regulatory T cells during active tuberculosis
Tuberculosis ( IF 3.2 ) Pub Date : 2021-09-14 , DOI: 10.1016/j.tube.2021.102126
Amare Kiflie 1 , Gezahegn Bewket 1 , Ebba Abate 1 , Thomas Schön 2 , Robert Blomgran 3
Affiliation  

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.



中文翻译:

无症状蛔虫、曼氏血吸虫或钩虫感染对活动性肺结核期间调节性 T 细胞频率和 TGF-β 产生能力的不同影响

蠕虫诱导的调节性 T 细胞 (Tregs) 扩增可能参与抑制结核病 (TB) 期间的保护性宿主反应,尽管 Tregs 的功能和与结核病严重程度的联系仍未探索。我们研究了蠕虫对 Treg 频率和 TGF-β 产生能力的物种特异性影响,以及与结核病严重程度的可能联系。包括来自埃塞俄比亚贡德尔的 89 名肺结核患者 (PTB) 和 69 名社区对照 (CC)。临床疾病严重程度通过 TB 评分进行分级,流式细胞术用于表征 Treg 频率和功能,测量其 TGF-β 产生能力。在蠕虫阳性 PTB 患者 (Helminth+PTB+) 中,与蠕虫阴性 PTB 或 CCs 相比,TGF-β + Tregs 主要在钩虫合并感染中显着增加,而S. mansoni增加了 CCs 中的 TGF-β + Tregs。在 2 个月的随访中,TB 和蠕虫的治疗降低了 Helminth+PTB+ 中的 TGF-β + Tregs。除非对 TB 疾病的严重程度进行分层,否则 CC 或 PTB 中 Treg 的频率没有总体差异。在纳入时,Helminth+PTB+ 已经增加了处于低疾病严重程度的 Tregs 的频率,并且 TGF-β + Tregs 与中高疾病严重程度相关。总之,PTB 患者中 TGF-β + Tregs 的蠕虫特异性增加与 TB 疾病严重程度相关,并在抗蠕虫治疗后恢复。

更新日期:2021-09-30
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