疟原虫来源MIF同源分子对DC功能的影响初探
发布时间：2018-07-14 07:55
【摘要】：疟疾是世界上最严重的传染性疾病之一,全球每年约有100万人死亡。一方面,疟疾的发病机理非常复杂,人们对其仍然缺乏了解。另一方面,迄今为止疟原虫逃逸宿主免疫攻击的机理还不清楚,并且目前没有任何疟原虫来源的分子被认为直接参与了对宿主免疫系统的调节。 MIF (Macrophage Migration Inhibitory Factor)是一种具有多种生物学活性的细胞因子,在细胞生长、分化、以及天然免疫和获得免疫中都具有重要的调节作用。研究发现,宿主来源的MIF在疟疾感染病理、特别是疟疾感染导致的贫血中发挥了重要作用。近年来,包括本实验室在内的三个研究小组先后报道了三个疟原虫来源的MIF分子：Plasmodium falciparum MIF (PfMIF), P.berghei MIF (PbMIF)和P.yoelii MIF (PyMIF)。结构和功能的初步研究结果显示,疟原虫来源的MIF结构保守,与宿主MIF的活性相似,具有调节宿主巨噬细胞的活性。但是,它如何调节宿主免疫系统、以及它在疟疾感染和病理过程所扮演的角色目前仍然不清楚。 本研究尝试研究约氏疟原虫MIF(PyMIF)对小鼠脾来源树突状细胞的调节效应,以宿主小鼠MIF分子作为对照,分别对脾DC识别和捕获抗原、成熟、对CD8+T细胞效应等过程进行了分析。实验结果显示：1)PyMIF可以显著下调脾DC表面的TLR4水平,影响脾DCs的吞噬功能,并不下调脾DCs表面的TLR2水平；2)不能促进未成熟小鼠脾来源树突状细胞的成熟,对CD8-CD4+CDIlb+ DCs及CD11c+CD8+DCs表面协同刺激分子CD40、CD80、CD86、MHCDⅠ、MHCⅡ表达均没有影响：3)PyMIF下调CD11c+CD8+ DCs的IL-12的表达,而上调TGF-β1的表达,但对CD8-CD4+CDllb+ DCs并无影响4)PyMIF通过脾DCs下调CD8+T细胞表面CD69的表达,通过CD11c+CD8+ DCs影响CD8+T分泌IL-2,但最终都不能影响CD8+T细胞的细胞杀伤功能。 以上结果说明PyMIF对脾DCs具有某些轻微的调节作用,CD11c+CD8+ DCs可能是PyMIF的靶细胞之一。
[Abstract]:Malaria is one of the most serious infectious diseases in the world, with about 1 million deaths a year worldwide. On the one hand, the pathogenesis of malaria is very complex, people still lack understanding of it. On the other hand, so far, the mechanism of immune attack by Plasmodium has not been clear. And there are no molecules from Plasmodium that are thought to be directly involved in regulating the host immune system. MIF (Macrophage Migration inhibitor Factor) is a cytokine with a variety of biological activities that grows and differentiates in cells. Both innate and acquired immunity play an important role in regulation. Host-derived MIF plays an important role in the pathogenesis of malaria infection, especially anemia caused by malaria infection. In recent years, three research groups, including our laboratory, have reported three MIF molecules: Plasmodium falciparum MIF (PfMIF), P.berghei MIF (PbMIF) and P.yoelii MIF (PyMIF) from three sources of Plasmodium plasmodium falciparum (PfMIF), P.berghei MIF (PbMIF) and P.yoelii MIF (PyMIF). The results of structural and functional studies showed that the MIF derived from Plasmodium was conserved, similar to the activity of host MIF, and had the ability to regulate macrophages. But how it regulates the host immune system and its role in malaria infection and pathology remains unclear. This study attempted to study the regulatory effects of Plasmodium yoelii MIF (PyMIF) on murine splenic dendritic cells. Using host mouse MIF molecules as control, the process of spleen DC recognition and capture antigen, maturation and CD8 T cell effect were analyzed respectively. The results showed that PyMIF could significantly down-regulate the level of TLR4 on the surface of splenic DCs and affect the phagocytic function of splenic DCs, but did not decrease the level of TLR2 on the surface of splenic DCs.) PyMIF could not promote the maturation of dendritic cells derived from the spleen of immature mice. On the surface of CD8-CD4 CDIlb DCs and CD11c CD8 DCs, the expression of CD40, CD80, CD86, MHCD 鈪，
本文编号：2120980
[Abstract]:Malaria is one of the most serious infectious diseases in the world, with about 1 million deaths a year worldwide. On the one hand, the pathogenesis of malaria is very complex, people still lack understanding of it. On the other hand, so far, the mechanism of immune attack by Plasmodium has not been clear. And there are no molecules from Plasmodium that are thought to be directly involved in regulating the host immune system. MIF (Macrophage Migration inhibitor Factor) is a cytokine with a variety of biological activities that grows and differentiates in cells. Both innate and acquired immunity play an important role in regulation. Host-derived MIF plays an important role in the pathogenesis of malaria infection, especially anemia caused by malaria infection. In recent years, three research groups, including our laboratory, have reported three MIF molecules: Plasmodium falciparum MIF (PfMIF), P.berghei MIF (PbMIF) and P.yoelii MIF (PyMIF) from three sources of Plasmodium plasmodium falciparum (PfMIF), P.berghei MIF (PbMIF) and P.yoelii MIF (PyMIF). The results of structural and functional studies showed that the MIF derived from Plasmodium was conserved, similar to the activity of host MIF, and had the ability to regulate macrophages. But how it regulates the host immune system and its role in malaria infection and pathology remains unclear. This study attempted to study the regulatory effects of Plasmodium yoelii MIF (PyMIF) on murine splenic dendritic cells. Using host mouse MIF molecules as control, the process of spleen DC recognition and capture antigen, maturation and CD8 T cell effect were analyzed respectively. The results showed that PyMIF could significantly down-regulate the level of TLR4 on the surface of splenic DCs and affect the phagocytic function of splenic DCs, but did not decrease the level of TLR2 on the surface of splenic DCs.) PyMIF could not promote the maturation of dendritic cells derived from the spleen of immature mice. On the surface of CD8-CD4 CDIlb DCs and CD11c CD8 DCs, the expression of CD40, CD80, CD86, MHCD 鈪，
本文编号：2120980
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