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体内诱导记忆样树突状细胞反应。

Induction of memory-like dendritic cell responses in vivo.

机构信息

Department of Biology, The University of Texas at San Antonio, San Antonio, TX, 78249, USA.

The South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, TX, 78249, USA.

出版信息

Nat Commun. 2019 Jul 4;10(1):2955. doi: 10.1038/s41467-019-10486-5.

Abstract

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.

摘要

树突状细胞(DCs)是先天免疫系统的重要组成部分,被认为缺乏抗原特异性并且没有免疫记忆。可以利用能够诱导先天细胞产生类似记忆反应的策略,在免疫功能低下的人群中引发保护性免疫。在这里,我们利用一种实验性免疫接种策略来调节针对机会性真菌病原体的 DC 炎症和类似记忆反应,该病原体在免疫功能低下的个体中会导致严重疾病。我们的结果表明,从保护性免疫的小鼠中分离出的 DCs 表现出干扰素和免疫信号通路的转录激活增强。我们还显示,在随后用真菌病原体进行挑战时,会产生类似长期记忆的细胞因子反应,而这些反应可以被特异性组蛋白修饰抑制剂所阻断。总之,我们的研究表明,可以设计免疫接种策略来引发针对传染病的类似记忆的 DC 反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6447/6609631/d54b58d743b4/41467_2019_10486_Fig1_HTML.jpg

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