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PLoS One:郑永唐等在恒河猴树突状细胞研究获进展

来源:中科院昆明动物研究所 2011-12-27 14:34

近日,国际著名杂志PLoS One在线刊登了中国科学院昆明动物研究所郑永唐研究员等的最新研究成果“Effect of Plasma Viremia on Apoptosis and Immunophenotype of Dendritic Cells Subsets in Acute SIVmac239 Infection of Chinese Rhesus Macaques。”文章中,研究者揭示了中国恒河猴SIV感染急性期树突状细胞研究的新进展。

灵长类动物模型对于艾滋病发病机制、治疗策略和疫苗的研究具有十分重要的意义。SIV或SHIV感染恒河猴模型是目前最为广泛应用的艾滋病动物模型。研究表明SIV感染中国恒河猴的疾病进程较印度恒河猴缓慢,更接近人艾滋病的发病进程。病毒感染早期的免疫活化可能是导致疾病进展快慢的主要原因之一。树突状细胞DC作为连接先天免疫和获得性免疫的重要抗原呈递细胞,在艾滋病发病进程中扮演着重要的角色。

中国科学院昆明动物研究所动物模型与人类疾病机理院重点实验室博士生夏厚军等人在导师郑永唐研究员的指导下,对SIVmac239感染中国恒河猴后树突状细胞亚群的数量、表型和功能变化及其机制进行了研究。前期研究发现浆细胞样DC (pDC)分泌IFN-α的能力在急性感染期会显著提高,提示SIVmac239感染的中国恒河猴在急性感染期提高了免疫活化,从而可能加速了疾病进程(Retrovirology, 2010, 7:102)。夏厚军等人在此基础上进一步研究了DC亚群在急性感染期的凋亡和免疫表型的改变。实验结果表明:病毒感染早期pDC由于高表达CD4和CCR5,可能成为SIV感染的主要靶细胞之一,其凋亡比例显著提高,而髓样DC (mDC) 的凋亡却没有显著变化,表明SIV很可能选择性地剔除pDC。同时,pDC的CD4表达随时间显著降低并与病毒载量呈负相关,pDC的CCR5表达却随时间而显著升高,并与病毒载量呈正相关。该现象暗示了SIV感染调节了pDC表面SIV受体的表达,也证实了pDC在SIV急性感染期扮演着十分重要的角色。在急性感染期,mDC和pDC的CD80和CD86表达均与病毒载量呈正相关,显示出DC亚群受病毒影响而处于活化状态,从而提升了整个机体的免疫活化,可能影响艾滋病的疾病进程。该研究也使得病毒感染早期pDC产生高水平的I型干扰素提高了免疫活化水平这一前期研究结果进一步得到了印证。

该研究得到国家科技重大专项、中国科学院和国家自然科学基金委的支持。(生物谷Bioon.com)

Effect of Plasma Viremia on Apoptosis and Immunophenotype of Dendritic Cells Subsets in Acute SIVmac239 Infection of Chinese Rhesus Macaques

Hou-Jun Xia1,3, Jian-Ping Ma1,3, Gao-Hong Zhang1, Jian-Bao Han1, Jian-Hua Wang2, Yong-Tang Zheng1*

Non-human primates such as Chinese rhesus macaques (Ch Rhs) provide good animal models for research on human infectious diseases. Similar to humans, there are two principal subsets of dendritic cells (DCs) in the peripheral blood of Ch Rhs: myeloid DCs (mDCs) and plasmacytoid DCs (pDCs). In this study, two-color fluorescence-activated cell sorting (FACS) analyses were used to identify the main DC subsets, namely CD1c+ mDCs and pDCs from Ch Rhs. Then, the apoptosis and immunophenotype changes of DCs subsets were first described during the acute phase of SIVmac239 infection. Both the DCs subsets showed decreased CD4 expression and enhanced CCR5 expression; in particular, those of pDCs significantly changed at most time points. Interestingly, the plasma viral loads were negatively correlated with CD4 expression, but were positively correlated with CCR5 expression of pDCs. During this period, both CD1c+ mDCs and pDCs were activated by enhancing expressions of co-stimulatory molecules, accompanied with increase in CCR7. Either CD80 or CD86 expressed on CD1c+ mDCs and pDCs was positively correlated with the plasma viral loads. Our analysis demonstrates that the pDCs were more prone to apoptosis after infection during the acute phase of SIVmac239 infection, which may be due to their high expressions of CD4 and CCR5. Both DCs subsets activated through elevating the expression of co-stimulatory molecules, which was beneficial in controlling the replication of SIV. However, a mere broad immune activation initiated by activated DCs may lead to tragic AIDS progression.

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