【摘要】：瘧疾是世界上最嚴(yán)重的傳染性疾病之一,全球每年約有100萬(wàn)人死亡。一方面,瘧疾的發(fā)病機(jī)理非常復(fù)雜,人們對(duì)其仍然缺乏了解。另一方面,迄今為止瘧原蟲逃逸宿主免疫攻擊的機(jī)理還不清楚,并且目前沒有任何瘧原蟲來(lái)源的分子被認(rèn)為直接參與了對(duì)宿主免疫系統(tǒng)的調(diào)節(jié)。 MIF (Macrophage Migration Inhibitory Factor)是一種具有多種生物學(xué)活性的細(xì)胞因子,在細(xì)胞生長(zhǎng)、分化、以及天然免疫和獲得免疫中都具有重要的調(diào)節(jié)作用。研究發(fā)現(xiàn),宿主來(lái)源的MIF在瘧疾感染病理、特別是瘧疾感染導(dǎo)致的貧血中發(fā)揮了重要作用。近年來(lái),包括本實(shí)驗(yàn)室在內(nèi)的三個(gè)研究小組先后報(bào)道了三個(gè)瘧原蟲來(lái)源的MIF分子：Plasmodium falciparum MIF (PfMIF), P.berghei MIF (PbMIF)和P.yoelii MIF (PyMIF)。結(jié)構(gòu)和功能的初步研究結(jié)果顯示,瘧原蟲來(lái)源的MIF結(jié)構(gòu)保守,與宿主MIF的活性相似,具有調(diào)節(jié)宿主巨噬細(xì)胞的活性。但是,它如何調(diào)節(jié)宿主免疫系統(tǒng)、以及它在瘧疾感染和病理過程所扮演的角色目前仍然不清楚。 本研究嘗試研究約氏瘧原蟲MIF(PyMIF)對(duì)小鼠脾來(lái)源樹突狀細(xì)胞的調(diào)節(jié)效應(yīng),以宿主小鼠MIF分子作為對(duì)照,分別對(duì)脾DC識(shí)別和捕獲抗原、成熟、對(duì)CD8+T細(xì)胞效應(yīng)等過程進(jìn)行了分析。實(shí)驗(yàn)結(jié)果顯示：1)PyMIF可以顯著下調(diào)脾DC表面的TLR4水平,影響脾DCs的吞噬功能,并不下調(diào)脾DCs表面的TLR2水平；2)不能促進(jìn)未成熟小鼠脾來(lái)源樹突狀細(xì)胞的成熟,對(duì)CD8-CD4+CDIlb+ DCs及CD11c+CD8+DCs表面協(xié)同刺激分子CD40、CD80、CD86、MHCDⅠ、MHCⅡ表達(dá)均沒有影響：3)PyMIF下調(diào)CD11c+CD8+ DCs的IL-12的表達(dá),而上調(diào)TGF-β1的表達(dá),但對(duì)CD8-CD4+CDllb+ DCs并無(wú)影響4)PyMIF通過脾DCs下調(diào)CD8+T細(xì)胞表面CD69的表達(dá),通過CD11c+CD8+ DCs影響CD8+T分泌IL-2,但最終都不能影響CD8+T細(xì)胞的細(xì)胞殺傷功能。 以上結(jié)果說明PyMIF對(duì)脾DCs具有某些輕微的調(diào)節(jié)作用,CD11c+CD8+ DCs可能是PyMIF的靶細(xì)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，

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