Wang Yuwei, Yang Chun, He Yonglin, Zhan Xingxing, Xu Lei
Department of Laboratory Medicine, Chongqing Hospital of Traditional Chinese Medicine, Chongqing 400021, P.R. China.
Department of Microbiology, Chongqing Medical University, Chongqing 400016, P.R. China.
Mol Med Rep. 2016 Aug;14(2):1756-64. doi: 10.3892/mmr.2016.5447. Epub 2016 Jun 27.
Tuberculosis is a major challenge to global public health. However, the Bacille Calmette‑Guérin (BCG), the only vaccine available against tuberculosis, has been questioned for the low protective effect. The present study used the mouse gene intracellular pathogen resistance I (Ipr1) gene to alter the current BCG vaccine and evaluated its immunity effect against tuberculosis. This study also investigated the intrinsic relationships of Ipr1 and innate immunity. The reformed BCG (BCGi) carrying the Ipr1 gene was constructed. The mice were intranasally challenged with the M. tuberculosis H37Rv strain after vaccination with BCGi. Protection efficacy of the vaccine was assessed by the organ coefficient, bacterial load and pathological changes in the lung. The differential expression of 113 immune‑related genes between BCGi and BCG groups were detected by an oligo microarray. According to the results of organ coefficient, bacterial load and pathological changes in the organization, BCGi had been shown to have stronger protective effects against M. tuberculosis than BCG. The oligo microarray and reverse transcription‑quantitative polymerase chain reaction further revealed that the Ipr1 gene could upregulate the expression of 13 genes, including a >3‑fold increase in Toll‑like receptor (TLR)4 and 10‑fold increase in surfactant protein D (sftpd). The two genes not only participate in innate immunity against pathogens, but also are closely interrelated. Ipr1 could activate the TLR4 and sftpd signaling pathway and improve the innate immunity against tuberculosis, therefore Ipr1 modified BCG may be a candidate vaccine against M. tuberculosis.
结核病是全球公共卫生面临的重大挑战。然而，目前唯一可用的抗结核疫苗卡介苗（BCG）的保护效果不佳，受到了质疑。本研究利用小鼠基因细胞内病原体抗性I（Ipr1）基因改造现有的卡介苗，并评估其对结核病的免疫效果。本研究还探究了Ipr1与天然免疫的内在关系。构建了携带Ipr1基因的重组卡介苗（BCGi）。用BCGi疫苗接种小鼠后，经鼻用结核分枝杆菌H37Rv菌株攻击。通过器官系数、细菌载量和肺部病理变化评估疫苗的保护效果。用寡核苷酸微阵列检测BCGi组和BCG组之间113个免疫相关基因的差异表达。根据组织器官系数、细菌载量和病理变化结果，BCGi对结核分枝杆菌的保护作用强于BCG。寡核苷酸微阵列及逆转录定量聚合酶链反应进一步显示，Ipr1基因可上调13个基因的表达，其中Toll样受体（TLR）4增加3倍以上，表面活性蛋白D（sftpd）增加10倍。这两个基因不仅参与针对病原体的天然免疫，而且密切相关。Ipr1可激活TLR4和sftpd信号通路，增强对结核病的天然免疫，因此Ipr1修饰的卡介苗可能是一种抗结核分枝杆菌的候选疫苗。
