小柯机器人

美国北卡罗来纳大学教堂山分校J. Victor Garcia和Angela Wahl共同合作，近期取得重要工作进展。他们研究发现，无菌人源化小鼠模型显示出常驻微生物群对人类特异性病原体感染的贡献。相关研究成果发表2023年8月10日在线发表于《自然—生物技术》杂志上。

据介绍，无细菌（GF）小鼠的固有微生物群已经耗尽，是探索微生物组在健康和疾病中作用的黄金标准。然而，它们在研究人类特定病原体方面的价值有限，因为不支持微生物的复制。

研究人员开发了用人类免疫细胞系统重组的GF小鼠，并用它们来评估常驻微生物组在两种人类特异性病原体EBV和HIV的获取、复制和发病机制中的作用。与传统（CV）人源化小鼠的比较表明，常驻微生物群增强了EBV感染和EBV诱导的肿瘤发生的建立，并增加了粘膜HIV的获取和复制。CV人源化小鼠的血浆和组织中的HIV RNA水平高于GF人源化鼠。在CV人源化小鼠中，整个肠道中CCR5⁺ CD4⁺ T细胞的频率也更高，这表明常驻微生物群控制着HIV靶细胞的水平。

因此，常驻微生物群促进了两种临床相关的人类特异性病原体的获得和发病机制。

附：英文原文

Title: A germ-free humanized mouse model shows the contribution of resident microbiota to human-specific pathogen infection

Author: Wahl, Angela, Yao, Wenbo, Liao, Baolin, Chateau, Morgan, Richardson, Cara, Ling, Lijun, Franks, Adrienne, Senthil, Krithika, Doyon, Genevieve, Li, Fengling, Frost, Josh, Whitehurst, Christopher B., Pagano, Joseph S., Fletcher, Craig A., Azcarate-Peril, M. Andrea, Hudgens, Michael G., Rogala, Allison R., Tucker, Joseph D., McGowan, Ian, Sartor, R. Balfour, Garcia, J. Victor

Issue&Volume: 2023-08-10

Abstract: Germ-free (GF) mice, which are depleted of their resident microbiota, are the gold standard for exploring the role of the microbiome in health and disease; however, they are of limited value in the study of human-specific pathogens because they do not support their replication. Here, we develop GF mice systemically reconstituted with human immune cells and use them to evaluate the role of the resident microbiome in the acquisition, replication and pathogenesis of two human-specific pathogens, Epstein–Barr virus (EBV) and human immunodeficiency virus (HIV). Comparison with conventional (CV) humanized mice showed that resident microbiota enhance the establishment of EBV infection and EBV-induced tumorigenesis and increase mucosal HIV acquisition and replication. HIV RNA levels were higher in plasma and tissues of CV humanized mice compared with GF humanized mice. The frequency of CCR5+ CD4+ T cells throughout the intestine was also higher in CV humanized mice, indicating that resident microbiota govern levels of HIV target cells. Thus, resident microbiota promote the acquisition and pathogenesis of two clinically relevant human-specific pathogens.

DOI: 10.1038/s41587-023-01906-5

Source: https://www.nature.com/articles/s41587-023-01906-5

Nature Biotechnology：《自然—生物技术》，创刊于1996年。隶属于施普林格·自然出版集团，最新IF：68.164
官方网址：https://www.nature.com/nbt/
投稿链接：https://mts-nbt.nature.com/cgi-bin/main.plex