近日，國際著名雜志PLoS One在線刊登了中國科學(xué)院昆明動(dòng)物研究所鄭永唐研究員等的最新研究成果“Effect of Plasma Viremia on Apoptosis and Immunophenotype of Dendritic Cells Subsets in Acute SIVmac239 Infection of Chinese Rhesus Macaques,。”文章中，研究者揭示了中國恒河猴SIV感染急性期樹突狀細(xì)胞研究的新進(jìn)展,。
靈長類動(dòng)物模型對(duì)于艾滋病發(fā)病機(jī)制、治療策略和疫苗的研究具有十分重要的意義,。SIV或SHIV感染恒河猴模型是目前最為廣泛應(yīng)用的艾滋病動(dòng)物模型,。研究表明SIV感染中國恒河猴的疾病進(jìn)程較印度恒河猴緩慢，更接近人艾滋病的發(fā)病進(jìn)程,。病毒感染早期的免疫活化可能是導(dǎo)致疾病進(jìn)展快慢的主要原因之一,。樹突狀細(xì)胞DC作為連接先天免疫和獲得性免疫的重要抗原呈遞細(xì)胞，在艾滋病發(fā)病進(jìn)程中扮演著重要的角色,。
中國科學(xué)院昆明動(dòng)物研究所動(dòng)物模型與人類疾病機(jī)理院重點(diǎn)實(shí)驗(yàn)室博士生夏厚軍等人在導(dǎo)師鄭永唐研究員的指導(dǎo)下,，對(duì)SIVmac239感染中國恒河猴后樹突狀細(xì)胞亞群的數(shù)量、表型和功能變化及其機(jī)制進(jìn)行了研究,。前期研究發(fā)現(xiàn)漿細(xì)胞樣DC (pDC）分泌IFN-α的能力在急性感染期會(huì)顯著提高,，提示SIVmac239感染的中國恒河猴在急性感染期提高了免疫活化，從而可能加速了疾病進(jìn)程(Retrovirology, 2010, 7:102),。夏厚軍等人在此基礎(chǔ)上進(jìn)一步研究了DC亞群在急性感染期的凋亡和免疫表型的改變,。實(shí)驗(yàn)結(jié)果表明：病毒感染早期pDC由于高表達(dá)CD4和CCR5，可能成為SIV感染的主要靶細(xì)胞之一,，其凋亡比例顯著提高,，而髓樣DC (mDC) 的凋亡卻沒有顯著變化,，表明SIV很可能選擇性地剔除pDC。同時(shí),，pDC的CD4表達(dá)隨時(shí)間顯著降低并與病毒載量呈負(fù)相關(guān),，pDC的CCR5表達(dá)卻隨時(shí)間而顯著升高，并與病毒載量呈正相關(guān),。該現(xiàn)象暗示了SIV感染調(diào)節(jié)了pDC表面SIV受體的表達(dá),，也證實(shí)了pDC在SIV急性感染期扮演著十分重要的角色。在急性感染期,，mDC和pDC的CD80和CD86表達(dá)均與病毒載量呈正相關(guān),，顯示出DC亞群受病毒影響而處于活化狀態(tài)，從而提升了整個(gè)機(jī)體的免疫活化,，可能影響艾滋病的疾病進(jìn)程,。該研究也使得病毒感染早期pDC產(chǎn)生高水平的I型干擾素提高了免疫活化水平這一前期研究結(jié)果進(jìn)一步得到了印證,。
該研究得到國家科技重大專項(xiàng),、中國科學(xué)院和國家自然科學(xué)基金委的支持。（生物谷Bioon.com）
doi:10.1371/journal.pone.0029036
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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.
