Clinical Bacteriology Section, Department of Infectious Medicine, Institute of Biomedicine, University of Gothenburg, Guldhedsgatan 10A, SE-413 46 Göteborg, Sweden.
Microbes Infect. 2012 Aug;14(9):768-77. doi: 10.1016/j.micinf.2012.03.005. Epub 2012 Mar 28.
The genus Mycobacterium includes obligate pathogens as well as opportunistic and non-pathogenic species ubiquitous in the environment. Mycobacteria have a unique cell wall abundant in lipids. Here we investigated cytokine production by human peripheral blood mononuclear cells (PBMC) in response to the opportunistic mycobacteria Mycobacterium avium and Mycobacterium abscessus, the non-pathogenic Mycobacterium gordonae and extracted surface lipids from the three species. The cytokine response elicited by mycobacteria, regardless of their pathogenic potential, differed distinctly from that induced by control Gram-positive (Enterococcus faecalis, Streptococcus mitis) and Gram-negative (Escherichia coli) bacteria. Mycobacteria induced no IL-12 and less TNF and IFN-γ compared with conventional Gram-positive bacteria. IL-10 was induced by all the mycobacteria and this production was partly responsible for the down-regulation of IL-12 and IFN-γ. The capacity of the Gram-positive bacterium E. faecalis to induce IL-12, as well as TNF and IFN-γ, in human PBMCs was strongly reduced when mycobacterial lipids were added. The mycobacterial surface lipids down-regulated the production of IL-12 and IFN-γ without eliciting IL-10 production. Our results show that mycobacteria evade triggering production of phagocyte activating cytokines (IL-12, TNF and IFN-γ) and that the mycobacterial cell wall surface lipids may play a significant role in this process.
分枝杆菌属包括专性病原体以及环境中普遍存在的机会性和非致病性物种。分枝杆菌具有独特的富含脂质的细胞壁。在这里,我们研究了人类外周血单核细胞(PBMC)对机会性分枝杆菌鸟分枝杆菌和脓肿分枝杆菌、非致病性戈登分枝杆菌以及从这三种细菌中提取的表面脂质的细胞因子产生。无论其致病性如何,分枝杆菌引起的细胞因子反应与对照革兰氏阳性(粪肠球菌、草绿色链球菌)和革兰氏阴性(大肠杆菌)细菌引起的反应明显不同。分枝杆菌与常规革兰氏阳性菌相比,不诱导 IL-12,TNF 和 IFN-γ 的产生也较少。所有分枝杆菌均诱导产生 IL-10,这部分导致了 IL-12 和 IFN-γ 的下调。当添加分枝杆菌脂质时,革兰氏阳性菌粪肠球菌在人类 PBMC 中诱导 IL-12 以及 TNF 和 IFN-γ 的能力大大降低。分枝杆菌表面脂质在不诱导产生 IL-10 的情况下下调了 IL-12 和 IFN-γ 的产生。我们的研究结果表明,分枝杆菌逃避触发吞噬细胞激活细胞因子(IL-12、TNF 和 IFN-γ)的产生,并且分枝杆菌细胞壁表面脂质可能在这一过程中发挥重要作用。