Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary, Cumming School of Medicine, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada.
Global Health Institute, Swiss Federal Institute of Technology, Lausanne, 1015 Lausanne, Switzerland; The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Immunity. 2022 Jul 12;55(7):1250-1267.e12. doi: 10.1016/j.immuni.2022.05.014. Epub 2022 Jun 15.
The intestine harbors a large population of resident eosinophils, yet the function of intestinal eosinophils has not been explored. Flow cytometry and whole-mount imaging identified eosinophils residing in the lamina propria along the length of the intestine prior to postnatal microbial colonization. Microscopy, transcriptomic analysis, and mass spectrometry of intestinal tissue revealed villus blunting, altered extracellular matrix, decreased epithelial cell turnover, increased gastrointestinal motility, and decreased lipid absorption in eosinophil-deficient mice. Mechanistically, intestinal epithelial cells released IL-33 in a microbiota-dependent manner, which led to eosinophil activation. The colonization of germ-free mice demonstrated that eosinophil activation in response to microbes regulated villous size alterations, macrophage maturation, epithelial barrier integrity, and intestinal transit. Collectively, our findings demonstrate a critical role for eosinophils in facilitating the mutualistic interactions between the host and microbiota and provide a rationale for the functional significance of their early life recruitment in the small intestine.
肠道中寄居着大量的常驻嗜酸性粒细胞，但肠道嗜酸性粒细胞的功能尚未得到探索。流式细胞术和全组织成像技术在出生后微生物定植前鉴定了定位于肠固有层的嗜酸性粒细胞。肠道组织的显微镜检查、转录组分析和质谱分析显示，在缺乏嗜酸性粒细胞的小鼠中，绒毛变钝、细胞外基质改变、上皮细胞更替减少、胃肠道蠕动增加和脂质吸收减少。从机制上讲，肠道上皮细胞以依赖于微生物的方式释放白细胞介素-33，从而导致嗜酸性粒细胞活化。无菌小鼠的定植表明，微生物激活嗜酸性粒细胞调节绒毛大小改变、巨噬细胞成熟、上皮屏障完整性和肠道转运。总的来说，我们的研究结果表明，嗜酸性粒细胞在促进宿主和微生物之间的共生相互作用方面发挥着关键作用，并为其在小肠中早期招募的功能意义提供了依据。
