白细胞介素 4 或干扰素-α诱导分化的树突状细胞中差异炎性体表达和白细胞介素 1β分泌。
Differential inflammasome expression and IL-1β secretion in monocyte-derived dendritic cells differentiated with IL-4 or IFN-α.
机构信息
Laboratory of Immunogenetics, Departament of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
出版信息
AIDS Res Ther. 2013 Dec 27;10(1):35. doi: 10.1186/1742-6405-10-35.
BACKGROUND
NLRP3-inflammasome activation was evaluated in monocyte-derived dendritic cells (DC) obtained through IL-4 (IL4-DC) or IFN-α (IFN-DC) protocols and pulsed with chemically inactivated HIV-1. Inflammasome' genes expression and IL-1β secretion were compared in DC isolated from 15 healthy subjects (HC) and 10 HIV-1 infected individuals (HIV+).
FINDINGS
Whether HIV was able to increased NLRP3-inflammasome genes expression and IL-1β secretion in IL4-DC from HC, the induction of inflammasome appeared significantly reduced in IFN-DC from HC, suggesting a different responsive state of IFN-DC compared to IL4-DC. No inflammasome activation was observed in IL4-DC as well as in IFN-DC derived from HIV + subjects, confirming previous findings on "unresponsive" state of DC derived from HIV + possibly due to chronic inflammatory state of these individuals.
CONCLUSIONS
Our results showed that IFN-α differently modulates inflammasome expression during monocytes-DC in vitro differentiation. These findings could be of interest considering the on-going research about DC manipulation and therapeutic strategies for HIV + involving DC-based immune-vaccines.
背景
通过白细胞介素 4（IL4-DC）或干扰素-α（IFN-DC）方案和用化学失活的 HIV-1 冲击，评估单核细胞来源的树突状细胞（DC）中 NLRP3-炎症小体的激活。比较了从 15 名健康受试者（HC）和 10 名 HIV-1 感染者（HIV+）中分离的 DC 中炎症小体基因表达和 IL-1β 分泌。
结果
尽管 HIV 是否能够增加 HC 的 IL4-DC 中的 NLRP3-炎症小体基因表达和 IL-1β 分泌，但在 HC 的 IFN-DC 中炎症小体的诱导明显减少，表明与 IL4-DC 相比，IFN-DC 具有不同的反应状态。在 HIV+受试者的 IL4-DC 和 IFN-DC 中均未观察到炎症小体激活，证实了先前关于 HIV+来源的 DC 处于“无反应”状态的发现，可能是由于这些个体的慢性炎症状态。
结论
我们的结果表明，IFN-α 在体外单核细胞-DC 分化过程中不同地调节炎症小体的表达。考虑到正在进行的关于涉及基于 DC 的免疫疫苗的 HIV+的 DC 操纵和治疗策略的研究，这些发现可能具有重要意义。
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