Coulter Felicity, Parrish Amy, Manning Declan, Kampmann Beate, Mendy Joseph, Garand Mathieu, Lewinsohn David M, Riley Eleanor M, Sutherland Jayne S
Vaccines and Immunity Theme, Medical Research Council Unit, Banjul, Gambia.
Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Front Immunol. 2017 Oct 11;8:1252. doi: 10.3389/fimmu.2017.01252. eCollection 2017.
IL-17-producing cells have been shown to be important in the early stages of (Mtb) infection in animal models. However, there are very little data on the role of IL-17 in human studies of tuberculosis (TB). We recruited TB patients and their highly exposed contacts who were further categorized based on results from an IFN-γ-release assay (IGRA): (1) IGRA positive (IGRA) at recruitment (latently TB infected), (2) IGRA negative (IGRA) at recruitment and 6 months [non-converters (NC)], and (3) IGRA at recruitment and IGRA at 6 months (converters). Whole blood was stimulated with mycobacterial antigens and analyzed using T helper (Th) 17 multiplex cytokine assays. Th17, Vγ9Vδ2, and CD161Vα7.2 mucosal-associated invariant T (MAIT) cells were analyzed by flow cytometry. The majority of IL-17 was produced by CD26CD4 Th17 cells (median 71%) followed by γδ T cells (6.4%) and MAIT cells (5.8%). TB patients had a significantly lower proportion of Th17 cells and CD4CD161Vα7.2 cells producing both IL-17 and IFN-γ compared to LTBI subjects. IGRA NC had significantly lower levels of CD26CD4 and CD8 MAIT cells producing IL-17 compared to IGRA C but had significantly higher levels of IL-17A, IL-17F, IL-21, and IL-23 in ESAT-6/CFP-10-stimulated supernatants compared to IGRA C. These data provide new insights into the role of IL-17 and IL-17-producing cells at three key stages of the Mtb infection spectrum.
在动物模型中，已证明产生白细胞介素 -17（IL -17）的细胞在结核分枝杆菌（Mtb）感染的早期阶段起重要作用。然而，关于IL -17在人类结核病（TB）研究中的作用，数据非常少。我们招募了结核病患者及其高暴露接触者，并根据干扰素 -γ释放试验（IGRA）结果进一步分类：（1）招募时IGRA阳性（IGRA）（潜伏性结核感染），（2）招募时和6个月时IGRA阴性（IGRA）[未转化者（NC）]，以及（3）招募时IGRA阴性而6个月时IGRA阳性（转化者）。用分枝杆菌抗原刺激全血，并使用辅助性T细胞（Th）17多重细胞因子检测进行分析。通过流式细胞术分析Th17、Vγ9Vδ2和CD161Vα7.2黏膜相关恒定T（MAIT）细胞。大多数IL -17由CD26CD4 Th17细胞产生（中位数71%），其次是γδT细胞（6.4%）和MAIT细胞（5.8%）。与潜伏性结核感染受试者相比，结核病患者产生IL -17和干扰素 -γ的Th17细胞及CD4CD161Vα7.2细胞的比例显著更低。与IGRA转化者相比，IGRA未转化者产生IL -17的CD26CD4和CD8 MAIT细胞水平显著更低，但与IGRA转化者相比，在早期分泌性抗原靶6 / 培养滤液蛋白10（ESAT -6/CFP -10）刺激的上清液中，IL -17A、IL -17F、IL -21和IL -23水平显著更高。这些数据为IL -17及产生IL -17的细胞在Mtb感染谱的三个关键阶段所起的作用提供了新的见解。
