Karolinska Institutet, Center for Infectious Medicine (CIM), F59, Department of Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden; Black Lion University Hospital and Addis Ababa University, Department of Pathology, Faculty of Medicine, Addis Ababa, Ethiopia.
Black Lion University Hospital and Addis Ababa University, Department of Internal Medicine, Faculty of Medicine, Addis Ababa, Ethiopia.
Clin Immunol. 2014 Apr;151(2):84-99. doi: 10.1016/j.clim.2014.01.010. Epub 2014 Feb 9.
In this study, we explored the local cytokine/chemokine profiles in patients with active pulmonary or pleural tuberculosis (TB) using multiplex protein analysis of bronchoalveolar lavage and pleural fluid samples. Despite increased pro-inflammation compared to the uninfected controls; there was no up-regulation of IFN-γ or the T cell chemoattractant CCL5 in the lung of patients with pulmonary TB. Instead, elevated levels of IL-4 and CCL4 were associated with high mycobacteria-specific IgG titres as well as SOCS3 (suppressors of cytokine signaling) mRNA and progression of moderate-to-severe disease. Contrary, IL-4, CCL4 and SOCS3 remained low in patients with extrapulmonary pleural TB, while IFN-γ, CCL5 and SOCS1 were up-regulated. Both SOCS molecules were induced in human macrophages infected with Mycobacterium tuberculosis in vitro. The Th2 immune response signature found in patients with progressive pulmonary TB could result from inappropriate cytokine/chemokine responses and excessive SOCS3 expression that may represent potential targets for clinical TB management.
在这项研究中，我们使用支气管肺泡灌洗液和胸腔液样本的多重蛋白质分析，来探索活动期肺部或胸膜结核（TB）患者的局部细胞因子/趋化因子谱。尽管与未感染对照相比，炎症反应增加，但在肺结核患者的肺部中，IFN-γ或 T 细胞趋化因子 CCL5 并没有上调。相反，IL-4 和 CCL4 的高水平与高结核分枝杆菌特异性 IgG 滴度以及 SOCS3（细胞因子信号转导抑制剂）mRNA 和中重度疾病的进展相关。相反，在患有肺外胸膜结核的患者中，IL-4、CCL4 和 SOCS3 仍然较低，而 IFN-γ、CCL5 和 SOCS1 则上调。体外感染结核分枝杆菌的人巨噬细胞中诱导了这两种 SOCS 分子。在进展性肺结核患者中发现的 Th2 免疫反应特征可能是由于不适当的细胞因子/趋化因子反应和 SOCS3 表达过度，这可能代表临床结核病管理的潜在靶点。
