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加蓬儿童中血吸虫和细菌TLR2配体的免疫活性

Immunologic activity of schistosomal and bacterial TLR2 ligands in Gabonese children.

作者信息

Retra K, van Riet E, Adegnika A A, Everts B, van Geest S, Kremsner P G, van Hellemond J J, van der Kleij D, Tielens A G M, Yazdanbakhsh M

机构信息

Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.

出版信息

Parasite Immunol. 2008 Jan;30(1):39-46. doi: 10.1111/j.1365-3024.2007.01000.x.

DOI:10.1111/j.1365-3024.2007.01000.x
PMID:18086015
Abstract

Schistosomes carry lipid moieties that interact with the immune system. To understand the consequence of interactions in terms of polarizing the cytokine profiles, the effect of two Toll-like receptor-2 (TLR2) activating schistosomal lipid fractions was studied on whole blood from Gabonese children living in a schistosomiasis endemic area. One fraction contained lysophosphatidylserine [monoacylglycerophosphoserine (lysoGPSer)] plus diacylphosphatidylserine [diacylglycerophosphoserine (GPSer)] while the other contained lysoGPSer and only a trace of GPSer. The effect of these schistosomal lipid fractions was compared with the known bacterial TLR2 ligands PAM3CSK4 and MALP-2. PAM3CSK4 and MALP-2 had preferential IL-10-activating capacities, while the fraction containing lysoGPSer plus GPSer had a strong TNF-alpha-inducing capacity. The fraction containing lysoGPSer was neutral with respect to pro- vs. anti-inflammatory effects. When Th1 and Th2 cytokines were analysed, the schistosomal lipid fraction containing lysoGPSer plus GPSer showed a stronger Th2 response compared to PAM3CSK4, MALP-2 and lysoGPSer alone. Therefore, the study indicates that not only TLR2 ligands derived from bacteria or from parasites can generate distinct cytokine profiles but also that the composition of lipid entities reaching the immune system can be important in leading to different immune outcomes. This information may be important for exploitation of immune modulatory molecules.

摘要

血吸虫携带与免疫系统相互作用的脂质部分。为了从细胞因子谱极化的角度理解这种相互作用的后果,研究了两种激活Toll样受体2(TLR2)的血吸虫脂质组分对生活在血吸虫病流行地区的加蓬儿童全血的影响。一种组分含有溶血磷脂酰丝氨酸[单酰甘油磷脂酰丝氨酸(lysoGPSer)]加二酰磷脂酰丝氨酸[二酰甘油磷脂酰丝氨酸(GPSer)],而另一种组分含有lysoGPSer且仅含有微量的GPSer。将这些血吸虫脂质组分的作用与已知的细菌TLR2配体PAM3CSK4和MALP-2进行了比较。PAM3CSK4和MALP-2具有优先激活IL-10的能力,而含有lysoGPSer加GPSer的组分具有很强的诱导TNF-α的能力。含有lysoGPSer的组分在促炎与抗炎作用方面呈中性。当分析Th1和Th2细胞因子时,与PAM3CSK4、MALP-2和单独的lysoGPSer相比,含有lysoGPSer加GPSer的血吸虫脂质组分显示出更强的Th2反应。因此,该研究表明,不仅源自细菌或寄生虫的TLR2配体可以产生不同的细胞因子谱,而且到达免疫系统的脂质实体的组成在导致不同的免疫结果方面可能很重要。这些信息对于免疫调节分子的开发可能很重要。

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