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视神经脊髓炎患者对大肠杆菌的体外免疫反应活性高与神经功能障碍和血浆脂多糖水平升高有关。

High in vitro immune reactivity to Escherichia coli in neuromyelitis optica patients is correlated with both neurological disabilities and elevated plasma lipopolysaccharide levels.

机构信息

Department of Microbiology and Parasitology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.

出版信息

Hum Immunol. 2013 Sep;74(9):1080-7. doi: 10.1016/j.humimm.2013.06.016. Epub 2013 Jun 15.

Abstract

The pathogenesis of neuromyelitis optica (NMO) is influenced by a combination of genetic and environmental factors, including infectious agents. Several infectious diseases can both trigger or exacerbate autoimmunity. The objective of the present work was to evaluate the in vitro immune responsiveness to Escherichia coli (EC), Staphylococcus aureus (SA) and Candida albicans (CA) in remittent-recurrent NMO patients, and correlate it with the level of neurological disability. Our results revealed that the extent of lymphoproliferation and cytokine profile in response to SA- and CA-stimulated PBMC cultures was similar between NMO patients and healthy individuals. Nevertheless, a higher in vitro CD4(+) T cell proliferation associated with elevated IL-1β, IL-6 and IL-17 release was observed in NMO-derived EC-stimulated cell cultures. Additionally, in these last cultures, the IL-10 production was significantly lower as compared with control group. The in vitro EC-induced levels of IL-6 and IL-17 were positively related with neurological disabilities. This higher tendency to produce Th17-related cytokines was proportional to the production of IL-23 and IL-6 by LPS-activated monocytes. Interestingly, elevated LPS levels were quantified in the plasma of NMO patients. The results suggest that a higher Th17-responsiveness to E. coli could be involved in the NMO pathogenesis.

摘要

视神经脊髓炎(NMO)的发病机制受遗传和环境因素(包括感染因子)的共同影响。一些传染病既能引发又能加重自身免疫。本研究旨在评估缓解-复发性 NMO 患者对大肠杆菌(EC)、金黄色葡萄球菌(SA)和白色念珠菌(CA)的体外免疫反应,并将其与神经功能缺损程度相关联。我们的结果表明,NMO 患者和健康个体的 SA 和 CA 刺激 PBMC 培养物中的淋巴细胞增殖和细胞因子谱相似。然而,在 NMO 来源的 EC 刺激细胞培养物中观察到与较高的 IL-1β、IL-6 和 IL-17 释放相关的体外 CD4+T 细胞增殖更高。此外,与对照组相比,这些培养物中的 IL-10 产生显著降低。体外 EC 诱导的 IL-6 和 IL-17 水平与神经功能障碍呈正相关。这种产生 Th17 相关细胞因子的较高趋势与 LPS 激活的单核细胞产生的 IL-23 和 IL-6 成比例。有趣的是,在 NMO 患者的血浆中定量了升高的 LPS 水平。结果表明,对大肠杆菌的更高 Th17 反应可能与 NMO 的发病机制有关。

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