Simian immunodeficiency virus infection potently modulates chemokine networks and immune environments in hilar lymph nodes of cynomolgus macaques.
Simian immunodeficiency virus infection potently modulates chemokine networks and immune environments in hilar lymph nodes of cynomolgus macaques.
复制标题
DOI：
10.1097/qai.0b013e31828ac85f
复制
发表时间：
2013-08-01
期刊：
影响因子：
--
通讯作者：
Reinhart TA
中科院分区：
文献类型：
--
作者：
Qin S;Junecko BA;Lucero CM;Klamar CR;Trichel AM;Murphey-Corb MA;Tarwater PM;Kirschner DE;Reinhart TA
趋化因子提供关键的免疫细胞归巢和激活信号，如果这些信号发生改变，可能会影响淋巴组织的炎症环境和细胞组成。在 HIV-1 和 SIV 感染期间，病毒会引发炎症/激活增加，导致免疫缺陷和机会性感染的发展，例如肺部——宿主与环境之间的巨大界面。采用实时 RT-PCR 和原位杂交技术测定 SIV/DeltaB670 感染后不同阶段食蟹猴肺门淋巴结中趋化因子、细胞因子和趋化因子受体的表达谱。使用组织切片的免疫染色和冷冻保存细胞的流式细胞术分析来检查淋巴结的细胞组成。 SIV感染后，肺门淋巴结中IFN-γ、1型趋化因子和同源趋化因子受体mRNA上调，而2型、稳态趋化因子和趋化因子受体mRNA下调。局部SIV和IFN-γ水平与1型趋化因子水平呈正相关，但与2型和稳态趋化因子水平呈负相关。利用原位杂交，在患有卡里氏肺孢子虫肺炎的动物的肺引流淋巴结中检测到了卡里氏肺孢子虫 rRNA。肺门淋巴结细胞组成的变化包括CD4+细胞和树突状细胞比例减少，CD8+、CXCR3+和CCR5+细胞比例增加。食蟹猴的 SIV 感染极大地改变了肺引流淋巴结的细胞归巢信号，这与免疫细胞组成的变化相关。这些变化可能导致免疫功能丧失，而免疫功能正是艾滋病的特征。
Chemokines provide critical immune cell homing and activation signals that if altered could affect the inflammatory milieu and cellular composition of lymphoid tissues. During HIV-1 and SIV infection, the virus triggers an increase in inflammation/activation, leading to immunodeficiency and development of opportunistic infections, such as in the lungs – a massive interface between the host and the environment. Chemokine, cytokine, and chemokine receptor expression profiles were determined using real-time RT-PCR and in situ hybridization in hilar lymph nodes from cynomolgus macaques at different stages after infection with SIV/DeltaB670. Immunostaining of tissue sections and flow cytometric analysis of cryopreserved cells were used to examine cellular compositions of lymph nodes. IFN-γ, type 1 chemokine and cognate chemokine receptor mRNAs were up-regulated, whereas type 2 and homeostatic chemokine and chemokine receptor mRNAs were down-regulated in hilar lymph nodes after SIV infection. Local SIV and IFN-γ levels were positively correlated with type 1 chemokine levels, but negatively correlated with type 2 and homeostatic chemokine levels. Using in situ hybridization, Pneumocystis carrini rRNA was detected in lung-draining lymph nodes from animals with P. carrini pneumonia. Changes in the cellular composition of hilar lymph nodes included decreased proportions of CD4+ cells and dendritic cells, and increased proportions of CD8+, CXCR3+ and CCR5+ cells. SIV infection of cynomolgus macaques dramatically alters the cellular homing signals of lung-draining lymph nodes, which correlated with changes in the immune cellular composition. These changes could contribute to the loss of immune function that defines AIDS.