Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses.
Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses.
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DOI：
10.1038/s41467-018-07478-2
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发表时间：
2018-11-28
影响因子：
16.6
通讯作者：
Ploss A
中科院分区：
文献类型：
--
作者：
Douam F;Ziegler CGK;Hrebikova G;Fant B;Leach R;Parsons L;Wang W;Gaska JM;Winer BY;Heller B;Shalek AK;Ploss A
移植人类免疫系统成分的小鼠已成为研究人类免疫和疾病方面的广泛使用的模型。然而，缺乏一种定义的方法来客观地测量和比较不同模型中人类免疫应答的质量。在这里，通过利用高免疫原性的黄热病减毒活疫苗YFV-17 D，我们提供了人类疫苗接种者、常规人源化小鼠和第二代人源化小鼠的免疫应答的深入比较。我们证明，人类骨髓和自然杀伤细胞的选择性扩增促进类似于人类疫苗的转录组反应。这些增强的转录谱与对YFV-17 D的抗原特异性细胞和体液应答的发展相关。总之，我们的方法提供了一个强大的评分的人源化小鼠的人类免疫应答的质量，并强调了一个合理的路径，以开发更好的临床前模型，用于研究人类免疫应答和疾病。人源化小鼠是一种探索人类免疫和疾病的技术。在这里，Douam等人提供了人类疫苗接种者、常规和第二代人源化小鼠对黄热病疫苗的免疫反应的深入比较，并定义了评估和完善这些模型的工作流程。
Mice engrafted with components of a human immune system have become widely-used models for studying aspects of human immunity and disease. However, a defined methodology to objectively measure and compare the quality of the human immune response in different models is lacking. Here, by taking advantage of the highly immunogenic live-attenuated yellow fever virus vaccine YFV-17D, we provide an in-depth comparison of immune responses in human vaccinees, conventional humanized mice, and second generation humanized mice. We demonstrate that selective expansion of human myeloid and natural killer cells promotes transcriptomic responses akin to those of human vaccinees. These enhanced transcriptomic profiles correlate with the development of an antigen-specific cellular and humoral response to YFV-17D. Altogether, our approach provides a robust scoring of the quality of the human immune response in humanized mice and highlights a rational path towards developing better pre-clinical models for studying the human immune response and disease. Humanized mice are an enabling technology to explore human immunity and disease. Here, Douam et al. provide an in-depth comparison of immune responses to yellow fever vaccine in human vaccinees, conventional and second-generation humanized mice and define a workflow to evaluate and refine these models.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
HIV-1对人源化BLT小鼠中功能性CD8⁺T细胞反应的快速演变。
影响因子：
17.1
作者：
Dudek TE;No DC;Seung E;Vrbanac VD;Fadda L;Bhoumik P;Boutwell CL;Power KA;Gladden AD;Battis L;Mellors EF;Tivey TR;Gao X;Altfeld M;Luster AD;Tager AM;Allen TM
通讯作者：
Allen TM
影响因子：
28.3
作者：
Chan KR;Wang X;Saron WAA;Gan ES;Tan HC;Mok DZL;Zhang SL;Lee YH;Liang C;Wijaya L;Ghosh S;Cheung YB;Tannenbaum SR;Abraham SN;St John AL;Low JGH;Ooi EE
通讯作者：
Ooi EE
影响因子：
5.4
作者：
Frias-Staheli, Natalia;Dorner, Marcus;Ploss, Alexander
通讯作者：
Ploss, Alexander
影响因子：
30.5
作者：
Huang, Li-Rung;Wohlleber, Dirk;Knolle, Percy A.
通讯作者：
Knolle, Percy A.