Lydia Becker Institute of Immunology and Inflammation, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
School of Life Sciences, University of Nottingham, Nottingham, UK.
Immunology. 2021 Dec;164(4):766-776. doi: 10.1111/imm.13413. Epub 2021 Sep 15.
With a long history of promoting pathological inflammation, eosinophils are now emerging as important regulatory cells. Yet, findings from controlled laboratory experiments so far lack translation to animals, including humans, in their natural environment. In order to appreciate the breadth of eosinophil phenotype under non-laboratory, uncontrolled conditions, we exploit a free-living population of the model organism Mus musculus domesticus. Eosinophils were present at significantly higher proportions in the spleen and bone marrow of wild mice compared with laboratory mice. Strikingly, the majority of eosinophils of wild mice exhibited a unique Ly6G phenotype seldom described in laboratory literature. Ly6G expression correlated with activation status in spleen and bone marrow, but not peritoneal exudate cells, and is therefore likely not an activation marker per se. Intermediate Ly6G expression was transiently induced in a small proportion of eosinophils from C57BL/6 laboratory mice during acute infection with the whipworm Trichuris muris, but not during low-dose chronic infection, which better represents parasite exposure in the wild. We conclude that the natural state of the eosinophil is not adequately reflected in the standard laboratory mouse, which compromises our attempts to dissect their functional relevance. Our findings emphasize the importance of studying the immune system in its natural context - alongside more mechanistic laboratory experiments - in order to capture the entirety of immune phenotypes and functions.
嗜酸性粒细胞在促进病理性炎症方面有着悠久的历史，现在它们正作为重要的调节细胞出现。然而，迄今为止，控制实验室实验的结果缺乏在其自然环境中的动物（包括人类）中的转化。为了在非实验室、不受控制的条件下欣赏嗜酸性粒细胞表型的广度，我们利用了模型生物小家鼠的自由生活种群。与实验室小鼠相比，野生小鼠的脾脏和骨髓中嗜酸性粒细胞的比例明显更高。引人注目的是，野生小鼠的大多数嗜酸性粒细胞表现出一种独特的 Ly6G 表型，在实验室文献中很少描述。Ly6G 的表达与脾脏和骨髓中的激活状态相关，但与腹膜渗出细胞无关，因此它本身可能不是激活标志物。在感染旋毛虫时，一小部分 C57BL/6 实验室小鼠的嗜酸性粒细胞中短暂诱导了中间 Ly6G 表达，但在低剂量慢性感染时没有，这更能代表野生环境中的寄生虫暴露。我们得出结论，嗜酸性粒细胞的自然状态在标准实验室小鼠中没有得到充分反映，这影响了我们对其功能相关性的研究。我们的研究结果强调了在其自然环境中研究免疫系统的重要性——与更具机制性的实验室实验相结合——以捕捉到免疫系统表型和功能的全貌。
