Institute of Medical Microbiology, Justus Liebig University, Frankfurter Str. 107, 35392 Giessen, Germany.
BMC Microbiol. 2010 Nov 2;10:275. doi: 10.1186/1471-2180-10-275.
We infected freshly isolated human peripheral monocytes with live bacteria of three clinically important gram-positive bacterial species, Staphylococcus aureus, Streptococcus pneumoniae and Listeria monocytogenes and studied the ensuing early transcriptional response using expression microarrays. Thus the observed response was unbiased by signals originating from other helper and effector cells of the host and was not limited to induction by solitary bacterial constituents.
Activation of monocytes was demonstrated by the upregulation of chemokine rather than interleukin genes except for the prominent expression of interleukin 23, marking it as the early lead cytokine. This activation was accompanied by cytoskeleton rearrangement signals and a general anti-oxidative stress and anti-apoptotic reaction. Remarkably, the expression profiles also provide evidence that monocytes participate in the regulation of angiogenesis and endothelial function in response to these pathogens.
Regardless of the invasion properties and survival mechanisms of the pathogens used, we found that the early response comprised of a consistent and common response. The common response was hallmarked by the upregulation of interleukin 23, a rather unexpected finding regarding Listeria infection, as this cytokine has been linked primarily to the control of extracellular bacterial dissemination.
我们用三种临床上重要的革兰氏阳性细菌,金黄色葡萄球菌、肺炎链球菌和单核细胞增生李斯特菌的活菌感染新分离的人外周血单核细胞,并使用表达微阵列研究随后的早期转录反应。因此,观察到的反应不受宿主其他辅助和效应细胞发出的信号的影响,并且不限于由单个细菌成分诱导。
除了白细胞介素 23 的明显表达,将其标记为早期领先细胞因子外,趋化因子而不是白细胞介素基因的上调证明了单核细胞的激活,这标志着单核细胞的激活。这种激活伴随着细胞骨架重排信号以及一般的抗氧化应激和抗细胞凋亡反应。值得注意的是,这些表达谱还提供了证据表明单核细胞参与了针对这些病原体的血管生成和内皮功能的调节。
无论使用的病原体的入侵特性和生存机制如何,我们发现早期反应包括一致和共同的反应。共同反应的特征是白细胞介素 23 的上调,这在李斯特菌感染方面是一个相当意外的发现,因为这种细胞因子主要与控制细胞外细菌扩散有关。