Transcriptional profiling of mycobacterial antigen-induced responses in infants vaccinated with BCG at birth.
Transcriptional profiling of mycobacterial antigen-induced responses in infants vaccinated with BCG at birth.
复制标题
DOI：
10.1186/1755-8794-2-10
复制
发表时间：
2009-02-24
影响因子：
2.7
通讯作者：
Hanekom WA
中科院分区：
文献类型：
--
作者：
Fletcher HA;Keyser A;Bowmaker M;Sayles PC;Kaplan G;Hussey G;Hill AV;Hanekom WA
最近在人类中测试的新型结核病（TB）疫苗旨在增强由当前疫苗（牛分枝杆菌卡介苗（BCG））诱导的免疫力。由于卡介苗接种广泛用于婴儿，这一人群可能是第一个进行新疫苗有效性试验的人群。然而，我们对婴儿对卡介苗免疫的复杂性的理解是不够的，这使得解释疫苗诱导的免疫反应变得困难。为了更好地了解卡介苗诱导的免疫力，我们对5名出生时常规接种卡介苗的10周龄婴儿进行了基因表达谱分析。从接种后10周收集的新生儿血液中分离的12小时BCG刺激的或结核菌素（PPD）刺激的PBMC的纯化蛋白衍生物中提取RNA。将RNA与Sentrix® HumanRef-8 Expression BeadChip（Illumina）杂交以测量> 16，000个基因的表达。我们发现用PPD和BCG离体刺激PBMC诱导了很大程度上相似的基因表达谱，除了BCG诱导了更大的巨噬细胞活化。过氧化物酶体增殖物激活受体（过氧化物酶体增殖物激活受体）信号通路（包括过氧化物酶体增殖物激活受体-γ）参与替代性抗炎巨噬细胞反应的激活，在两种抗原刺激后下调。相反，与经典的促炎性巨噬细胞反应相关的基因上调。进一步的分析显示细胞粘附分子（CAM）的表达减少，包括整合素α M（ITGAM），已知其对分枝杆菌进入巨噬细胞很重要。有趣的是，更多的白细胞基因被下调比上调。我们的研究结果表明，抑制和上调基因的组合可能是决定卡介苗接种诱导的结核病保护性免疫发展的关键。
Novel tuberculosis (TB) vaccines recently tested in humans have been designed to boost immunity induced by the current vaccine, Mycobacterium bovis Bacille Calmette-Guérin (BCG). Because BCG vaccination is used extensively in infants, this population group is likely to be the first in which efficacy trials of new vaccines will be conducted. However, our understanding of the complexity of immunity to BCG in infants is inadequate, making interpretation of vaccine-induced immune responses difficult. To better understand BCG-induced immunity, we performed gene expression profiling in five 10-week old infants routinely vaccinated with BCG at birth. RNA was extracted from 12 hour BCG-stimulated or purified protein derivative of tuberculin (PPD)-stimulated PBMC, isolated from neonatal blood collected 10 weeks after vaccination. RNA was hybridised to the Sentrix® HumanRef-8 Expression BeadChip (Illumina) to measure expression of >16,000 genes. We found that ex vivo stimulation of PBMC with PPD and BCG induced largely similar gene expression profiles, except that BCG induced greater macrophage activation. The peroxisome proliferator-activated receptor (PPAR) signaling pathway, including PPAR-γ, involved in activation of the alternative, anti-inflammatory macrophage response was down-regulated following stimulation with both antigens. In contrast, up-regulation of genes associated with the classic, pro-inflammatory macrophage response was noted. Further analysis revealed a decrease in the expression of cell adhesion molecules (CAMs), including integrin alpha M (ITGAM), which is known to be important for entry of mycobacteria into the macrophage. Interestingly, more leukocyte genes were down-regulated than up-regulated. Our results suggest that a combination of suppressed and up-regulated genes may be key in determining development of protective immunity to TB induced by vaccination with BCG.
登录
查看更多内容
影响因子：
3.8
作者：
Kawada, Jun-ichi;Kimura, Hiroshi;Morishima, Tsuneo
通讯作者：
Morishima, Tsuneo
影响因子：
1.8
作者：
Meade, Kieran G.;Gormley, Eamonn;MacHugh, David E.
通讯作者：
MacHugh, David E.
影响因子：
15.9
作者：
Shum, Bennett O. V.;Mackay, Charles R.;Rolph, Michael S.
通讯作者：
Rolph, Michael S.
影响因子：
20.3
作者：
Ramilo, Octavio;Allman, Windy;Chaussabel, Damien
通讯作者：
Chaussabel, Damien
影响因子：
29
作者：
Bouhlel, M. Amine;Derudas, Bruno;Chinetti-Gbaguidi, Giulia
通讯作者：
Chinetti-Gbaguidi, Giulia