Disparate effects of acute and chronic infection with SIVmac239 or SHIV-89.6P on macaque plasmacytoid dendritic cells.
Disparate effects of acute and chronic infection with SIVmac239 or SHIV-89.6P on macaque plasmacytoid dendritic cells.
复制标题
DOI：
10.1016/j.virol.2007.03.055
复制
发表时间：
2007-09-01
期刊：
影响因子：
3.7
通讯作者：
Fultz, Patricia N.
中科院分区：
文献类型：
--
作者：
Reeves, R. Keith;Fultz, Patricia N.
血浆细胞样树突状细胞（Blood plasmacytoid dendritic cells，pDC）通过在急性细菌和病毒感染后分泌高水平的IFN-α和间接增强细胞介导的免疫而参与先天性和适应性免疫应答。横断面研究表明，与未感染个体相比，HIV患者中循环pDC的数量减少。然而，由于HIV感染患者的感染时间通常是未知的，因此对病毒暴露后立即发生的pDC-病毒相互作用知之甚少。目前的研究调查了猕猴急性和慢性感染SIVmac 239或致病性SIV-HIV嵌合体SHIV-89.6P期间的pDC动力学，作为HIV感染的模型。在静脉注射SIVmac 239感染的三只恒河猴和三只猪尾猕猴中，血液中pDC的百分比在感染后的前6周内下降2至6倍，并在整个病程中保持抑制。令人惊讶的是，在六只感染SHIV-89.6P的猕猴中没有观察到外周血pDC的一致的、可比较的下降。在后一组中，pDC的百分比与CD 4 + T细胞无关，但与病毒载量呈负相关。此外，与未感染的对照组相比，SIVmac 239感染的动物的脾脏和外周淋巴结中pDC的百分比降低，而SHIV-89. 6P感染的动物的脾脏和外周淋巴结中pDC的百分比没有降低。在从感染任一病毒的猕猴分离的pDC中的急性期期间检测到前病毒DNA。这些结果意味着，即使猕猴pDC可以被SIVmac 239和SHIV-89.6P感染，但随后对体内发病机制的影响不同。这些差异的潜在机制尚不清楚，但选择SIV或SHIV作为攻毒病毒可能会影响一些研究的结果，例如评估疫苗或药物治疗效果的研究。
Blood plasmacytoid dendritic cells (pDCs) contribute to both innate and adaptive immune responses by secreting high levels of IFN-α following acute bacterial and viral infections and indirectly by augmenting cell-mediated immunity. Cross-sectional studies have shown that the number of circulating pDCs in HIV patients, compared to that in uninfected individuals, is reduced. However, since the time of infection is usually unknown in HIV-infected patients, pDC–virus interactions that occur immediately after virus exposure are poorly understood. The current study investigated pDC dynamics during acute and chronic infections of macaques with either SIVmac239 or the pathogenic SIV–HIV chimera, SHIV-89.6P, as models for HIV infection. In three rhesus and three pig-tailed macaques infected intravenously with SIVmac239, the percentages of pDCs in blood declined 2- to 6-fold during the first 6 weeks after infection and remained depressed throughout the disease course. Surprisingly, no consistent, comparable decline in peripheral blood pDCs was observed in six macaques infected with SHIV-89.6P. In this latter group, percentages of pDCs did not correlate with CD4+ T cells, but there was an inverse relationship with viral load. In addition, when compared to naïve controls, the percentages of pDCs were reduced in spleens and peripheral lymph nodes of SIVmac239- but not SHIV-89.6P-infected animals that had progressed to AIDS. Proviral DNA was detected during the acute phase in pDCs isolated from macaques infected with either virus. These results imply that, even though macaque pDCs can be infected by both SIVmac239 and SHIV-89.6P, the subsequent effects on in vivo pathogenesis differ. The underlying mechanism(s) for these differences is unclear, but the selection of SIV or SHIV as a challenge virus might influence the outcome of some studies, such as those evaluating vaccines or the therapeutic efficacy of drugs.
登录
查看更多内容
影响因子：
9.1
作者：
Duan, XZ;Wang, M;Wang, FS
通讯作者：
Wang, FS
影响因子：
4.4
作者：
Fanning, Stacey L.;George, Thaddeus C.;Fitzgerald-Bocarsly, Patricia
通讯作者：
Fitzgerald-Bocarsly, Patricia
影响因子：
15.9
作者：
Beignon, AS;McKenna, K;Bhardwaj, N
通讯作者：
Bhardwaj, N
影响因子：
20.3
作者：
Donaghy, H;Gazzard, B;Patterson, S
通讯作者：
Patterson, S
影响因子：
5.4
作者：
Fonteneau, JF;Larsson, M;Bhardwaj, N
通讯作者：
Bhardwaj, N