Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
Hospital for Tropical Diseases, University College Hospital, and Clinical Research Department, London School of Hygiene and Tropical Medicine, London, UK.
Eur J Immunol. 2016 Mar;46(3):752-61. doi: 10.1002/eji.201545843. Epub 2016 Jan 11.
In many settings, adults with active or latent tuberculosis will also be coinfected with helminths. Our study aimed to investigate how anthelmintic treatment modulates antimycobacterial immunity, in a setting where helminth reinfection should not occur. We investigated the potential impact of helminth infection on immune responses to Mycobacterium tuberculosis (Mtb) in patients with latent Mtb infection with or without helminth infection (Strongyloides or Schistosoma), and tested T-cell responses before and after anthelmintic treatment. The study was performed in migrants resident in the United Kingdom, where reexposure and reinfection following anthelmintic treatment would not occur. The frequency of CD4(+) IFN-γ(+) T cells was measured following stimulation with Mtb Purified Protein Derivative or ESAT-6/CFP-10 antigen, and concentrations of IFN-γ in culture supernatants measured by ELISA and multiplex bead array. Helminth infection was associated with a lower frequency of CD4(+) IFN-γ(+) T cells, which increased following treatment. Patients with helminth infection showed a significant increase in CD4(+) FoxP3(+) T cells (Treg) compared to those without helminth infection. There was a decrease in the frequency of Treg cells, and an associated increase in CD4(+) IFN-γ(+) T cells after the anthelmintic treatment. Here, we show a potential role of Treg cells in reducing the frequency and function of antimycobacterial CD4(+) IFN-γ(+) T cells, and that these effects are reversed after anthelmintic treatment.
在许多情况下,患有活动性或潜伏性结核病的成年人也会同时感染寄生虫。我们的研究旨在探讨驱虫治疗如何调节抗分枝杆菌免疫,特别是在寄生虫不会再次感染的情况下。我们研究了寄生虫感染对潜伏性结核分枝杆菌(Mtb)感染患者(有无寄生虫感染,如钩虫或血吸虫)的免疫反应的潜在影响,并在驱虫治疗前后测试了 T 细胞反应。该研究在居住在英国的移民中进行,在这些人中,驱虫治疗后不会再次暴露和再次感染寄生虫。采用酶联免疫吸附试验和多重珠阵列法,通过刺激 Mtb 纯化蛋白衍生物或 ESAT-6/CFP-10 抗原来测量 CD4+IFN-γ+T 细胞的频率,并测量培养上清液中 IFN-γ的浓度。寄生虫感染与 CD4+IFN-γ+T 细胞的频率较低有关,而治疗后这种频率增加。与无寄生虫感染的患者相比,寄生虫感染的患者显示 CD4+FoxP3+T 细胞(Treg)的频率显著增加。驱虫治疗后,Treg 细胞的频率降低,同时 CD4+IFN-γ+T 细胞的频率增加。在这里,我们显示 Treg 细胞在降低抗分枝杆菌 CD4+IFN-γ+T 细胞的频率和功能方面具有潜在作用,并且这些作用在驱虫治疗后被逆转。