Department of Internal Medicine, Radboud Institute of Molecular Life Sciences (RIMLS), and Radboud Center of Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Pathology and Molecular Medicine, University of Otago, Wellington, Wellington, New Zealand.
J Leukoc Biol. 2020 Jan;107(1):113-118. doi: 10.1002/JLB.4AB0219-071R. Epub 2019 Aug 4.
Studies in IL-32 transgenic mice and in vitro suggest that IL-32 may have protective effects against Mycobacterium tuberculosis, but so far there are barely any studies in humans. We studied the role of IL-32 and its splice variants in tuberculosis (TB) in vivo and in vitro. Blood transcriptional analysis showed lower total IL-32 mRNA levels in pulmonary TB patients compared to patients with latent TB infection and healthy controls. Also, among Indonesian household contacts who were heavily exposed to an infectious TB patient, IL-32 mRNA levels were higher among those who remained uninfected compared to those who became infected with M. tuberculosis. In peripheral blood mononuclear cells from healthy donors, we found that IL-32γ, the most potent isoform, was down-regulated upon M. tuberculosis stimulation. This decrease in IL-32γ was mirrored by an increase of another splice variant, IL-32β. Also, a higher IL-32γ/IL-32β ratio correlated with IFN-γ production, whereas a lower ratio correlated with production of IL-1Ra, IL-6, and IL-17. These data suggest that IL-32 contributes to protection against M. tuberculosis infection, and that this effect may depend on the relative abundance of different IL-32 isoforms.
在 IL-32 转基因小鼠和体外研究中表明，IL-32 可能对结核分枝杆菌具有保护作用，但到目前为止，人类几乎没有相关研究。我们研究了 IL-32 及其剪接变异体在体内和体外结核病（TB）中的作用。血液转录分析显示，与潜伏性结核感染患者和健康对照组相比，肺结核患者的总 IL-32 mRNA 水平较低。此外，在与传染性结核患者密切接触的印度尼西亚家庭接触者中，与感染结核分枝杆菌的接触者相比，未感染者的 IL-32 mRNA 水平更高。在健康供体的外周血单核细胞中，我们发现最有效的同工型 IL-32γ 在结核分枝杆菌刺激后下调。IL-32γ 的这种减少与另一种剪接变异体 IL-32β 的增加相匹配。此外，较高的 IL-32γ/IL-32β 比值与 IFN-γ 产生相关，而较低的比值与 IL-1Ra、IL-6 和 IL-17 的产生相关。这些数据表明，IL-32 有助于预防结核分枝杆菌感染，并且这种作用可能取决于不同 IL-32 同工型的相对丰度。
