Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada ; Research Institute, McGill University Health Centre, Montreal, Quebec, Canada.
PLoS One. 2013 Oct 16;8(10):e78146. doi: 10.1371/journal.pone.0078146. eCollection 2013.
Tryptophan (Trp) catabolism into immunosuppressive kynurenine (Kyn) by indoleamine 2,3-dioxygenase (IDO) was previously linked to Th17/Treg differentiation and immune activation. Here we examined Trp catabolism and its impact on Th17/Treg balance in uninfected healthy subjects (HS) and a large cohort of HIV-infected patients with different clinical outcomes: ART-naïve, Successfully Treated (ST), and elite controllers (EC). In ART-naïve patients, increased IDO activity/expression, together with elevated levels of TNF-α and sCD40L, were associated with Treg expansion and an altered Th17/Treg balance. These alterations were normalized under ART. In contrast, Trp 2,3-dioxegenase (TDO) expression was dramatically lower in EC when compared to all other groups. Interestingly, EC displayed a distinctive Trp metabolism characterized by low Trp plasma levels similar to ART-naïve patients without accumulating immunosuppressive Kyn levels which was accompanied by a preserved Th17/Treg balance. These results suggest a distinctive Trp catabolism and Th17/Treg balance in HIV progressors and EC. Thus, IDO-induced immune-metabolism may be considered as a new inflammation-related marker for HIV-1 disease progression.
色氨酸（Trp）通过吲哚胺 2,3-双加氧酶（IDO）代谢为免疫抑制性犬尿氨酸（Kyn），先前与 Th17/Treg 分化和免疫激活有关。在这里，我们研究了未感染的健康受试者（HS）和不同临床结局的大量 HIV 感染患者中色氨酸代谢及其对 Th17/Treg 平衡的影响：未经抗逆转录病毒治疗（ART）、成功治疗（ST）和精英控制者（EC）。在未经 ART 治疗的患者中，IDO 活性/表达增加，以及 TNF-α 和 sCD40L 水平升高，与 Treg 扩增和 Th17/Treg 平衡改变有关。这些变化在接受 ART 治疗后得到了纠正。相比之下，与其他所有组相比，EC 中的 Trp 2,3-双加氧酶（TDO）表达显著降低。有趣的是，EC 表现出独特的色氨酸代谢特征，其色氨酸血浆水平较低，类似于未经 ART 治疗的患者，但不会累积免疫抑制性 Kyn 水平，同时保持 Th17/Treg 平衡。这些结果表明，HIV 进展者和 EC 中存在独特的色氨酸代谢和 Th17/Treg 平衡。因此，IDO 诱导的免疫代谢可被视为 HIV-1 疾病进展的一个新的与炎症相关的标志物。
