Free-living mammals, such as humans and wild mice, display heightened immune activation compared with artificially maintained laboratory mice. These differences are partially attributed to microbial exposure as laboratory mice infected with pathogens exhibit immune profiles more closely resembling that of free-living animals. Here, we examine how colonization by microorganisms within the natural environment contributes to immune system maturation by releasing inbred laboratory mice into an outdoor enclosure. In addition to enhancing differentiation of T cell populations previously associated with pathogen exposure, outdoor release increased circulating granulocytes. However, these "rewilded" mice were not infected by pathogens previously implicated in immune activation. Rather, immune system changes were associated with altered microbiota composition with notable increases in intestinal fungi. Fungi isolated from rewilded mice were sufficient in increasing circulating granulocytes. These findings establish a model to investigate how the natural environment impacts immune development and show that sustained fungal exposure impacts granulocyte numbers.

中文翻译：

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自然环境下实验小鼠免疫力的改变与真菌定植有关。

与人工维护的实验室小鼠相比，诸如人类和野生小鼠等自由活动的哺乳动物显示出更高的免疫激活能力。这些差异部分归因于微生物暴露，因为感染病原体的实验室小鼠的免疫特性与自由生活动物的相似。在这里，我们研究了自然环境中微生物的定殖如何通过将近交实验室小鼠释放到室外环境中来促进免疫系统的成熟。除了增强以前与病原体暴露相关的T细胞群体的分化外，室外释放还增加了循环中的粒细胞。但是，这些“迷茫的”小鼠没有被先前与免疫激活有关的病原体感染。而是 免疫系统的变化与微生物群组成的改变以及肠道真菌的显着增加有关。从野生小鼠中分离出的真菌足以增加循环中的粒细胞。这些发现建立了一个模型，以研究自然环境如何影响免疫发育，并表明持续的真菌暴露会影响粒细胞的数量。