PDF(Pubmed)
Abstract：
The discovery of promising cytokines and clarification of their immunological mechanisms in controlling the intracellular fate of Mycobacterium tuberculosis (Mtb) are necessary to identify effective diagnostic biomarkers and therapeutic targets. To escape immune clearance, Mtb can manipulate and inhibit the normal host process of phagosome maturation. Phagosome maturation arrest by Mtb involves multiple effectors and much remains unknown about this important aspect of Mtb pathogenesis. In this study, we found that interleukin 16 (IL-16) is elevated in the serum samples of Tuberculosis (TB) patients and can serve as a specific target for treatment TB. There was a significant difference in IL-16 levels among active TB, latent TB infection (LTBI), and non-TB patients. This study first revealed that macrophages are the major source of IL-16 production in response to Mtb infection, and elucidated that IL-16 can promote Mtb intracellular survival by inhibiting phagosome maturation and suppressing the expression of Rev-erbα which can inhibit IL-10 secretion. The experiments using zebrafish larvae infected with M. marinum and mice challenged with H37Rv demonstrated that reducing IL-16 levels resulted in less severe pathology and improved survival, respectively. In conclusion, this study provided direct evidence that Mtb hijacks the host macrophages-derived interleukin 16 to enhance intracellular growth. It is suggesting the immunosuppressive role of IL-16 during Mtb infection, supporting IL-16 as a promising therapeutic target.
摘要：
有希望的细胞因子的发现及其在控制结核分枝杆菌（Mtb）的细胞内命运中的免疫学机制的阐明对于确定有效的诊断生物标志物和治疗靶标是必要的。为了逃避免疫清除，Mtb可以操纵和抑制吞噬体成熟的正常宿主过程。Mtb的吞噬体成熟停滞涉及多种效应物，关于Mtb发病机理的这一重要方面仍不清楚。在这项研究中,我们发现白细胞介素16（IL-16）在结核病（TB）患者的血清样本中升高，可以作为结核病治疗的特定靶标。在活动性TB中IL-16水平存在显著差异,潜伏性结核感染（LTBI），和非结核病患者。这项研究首次揭示，巨噬细胞是响应Mtb感染产生IL-16的主要来源，并阐明IL-16可以通过抑制吞噬体成熟和抑制可以抑制IL-10分泌的Rev-erbα的表达来促进Mtb细胞内存活。使用感染M.marinum的斑马鱼幼虫和用H37Rv攻击的小鼠的实验表明，降低IL-16水平可降低严重的病理学并提高生存率，分别。总之,这项研究提供了直接证据,表明Mtb劫持宿主巨噬细胞衍生的白细胞介素16以促进细胞内生长.这表明IL-16在Mtb感染期间的免疫抑制作用，支持IL-16作为有前途的治疗靶标。
