Induction of memory-like dendritic cell responses in vivo

Induction of memory-like dendritic cell responses in vivo
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DOI:
10.1038/s41467-019-10486-5
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发表时间:
2019-07-04
影响因子:
16.6
通讯作者:
Wormley, Floyd L., Jr.
Wormley, Floyd L., Jr.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Hole, Camaron R.;Wager, Chrissy M. Leopold;Wormley, Floyd L., Jr.

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树突状细胞(Dendritic cells,DCs)是先天免疫系统的重要组成部分,但缺乏抗原特异性和免疫记忆。可以从先天细胞诱导记忆样反应的策略可以用于在免疫缺陷的人中引发保护性免疫。在这里,我们利用实验性免疫策略来调节DC炎症和记忆样反应,以对抗在免疫功能低下的个体中引起显著疾病的机会性真菌病原体。我们的研究结果表明,从保护性免疫小鼠中分离的DC表现出增强的干扰素和免疫信号转导通路的转录激活。我们还显示了长期的记忆样细胞因子反应后,随后的挑战与真菌病原体被废除与特定组蛋白修饰的抑制剂。总之,我们的研究表明,免疫策略可以被设计为引起记忆样DC响应对传染病。
Dendritic cells (DCs), a vital component of the innate immune system, are considered to lack antigen specificity and be devoid of immunological memory. Strategies that can induce memory-like responses from innate cells can be utilized to elicit protective immunity in immune deficient persons. Here we utilize an experimental immunization strategy to modulate DC inflammatory and memory-like responses against an opportunistic fungal pathogen that causes significant disease in immunocompromised individuals. Our results show that DCs isolated from protectively immunized mice exhibit enhanced transcriptional activation of interferon and immune signaling pathways. We also show long-term memory-like cytokine responses upon subsequent challenge with the fungal pathogen that are abrogated with inhibitors of specific histone modifications. Altogether, our study demonstrates that immunization strategies can be designed to elicit memory-like DC responses against infectious disease.