Kanther Michelle, Tomkovich Sarah, Xiaolun Sun, Grosser Melinda R, Koo Jaseol, Flynn Edward J, Jobin Christian, Rawls John F
Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC, 27599, USA.
Cell Microbiol. 2014 Jul;16(7):1053-67. doi: 10.1111/cmi.12257. Epub 2014 Jan 24.
Neutrophils serve critical roles in inflammatory responses to infection and injury, and mechanisms governing their activity represent attractive targets for controlling inflammation. The commensal microbiota is known to regulate the activity of neutrophils and other leucocytes in the intestine, but the systemic impact of the microbiota on neutrophils remains unknown. Here we utilized in vivo imaging in gnotobiotic zebrafish to reveal diverse effects of microbiota colonization on systemic neutrophil development and function. The presence of a microbiota resulted in increased neutrophil number and myeloperoxidase expression, and altered neutrophil localization and migratory behaviours. These effects of the microbiota on neutrophil homeostasis were accompanied by an increased recruitment of neutrophils to injury. Genetic analysis identified the microbiota-induced acute phase protein serum amyloid A (Saa) as a host factor mediating microbial stimulation of tissue-specific neutrophil migratory behaviours. In vitro studies revealed that zebrafish cells respond to Saa exposure by activating NF-κB, and that Saa-dependent neutrophil migration requires NF-κB-dependent gene expression. These results implicate the commensal microbiota as an important environmental factor regulating diverse aspects of systemic neutrophil development and function, and reveal a critical role for a Saa-NF-κB signalling axis in mediating neutrophil migratory responses.
中性粒细胞在对感染和损伤的炎症反应中发挥关键作用，而调控其活性的机制是控制炎症的有吸引力的靶点。已知共生微生物群可调节肠道中中性粒细胞和其他白细胞的活性，但微生物群对中性粒细胞的全身影响仍不清楚。在这里，我们利用无菌斑马鱼的体内成像来揭示微生物群定殖对全身中性粒细胞发育和功能的多种影响。微生物群的存在导致中性粒细胞数量增加和髓过氧化物酶表达增加，并改变了中性粒细胞的定位和迁移行为。微生物群对中性粒细胞稳态的这些影响伴随着中性粒细胞向损伤部位募集的增加。基因分析确定微生物群诱导的急性期蛋白血清淀粉样蛋白A（Saa）是介导微生物刺激组织特异性中性粒细胞迁移行为的宿主因子。体外研究表明，斑马鱼细胞通过激活NF-κB对Saa暴露作出反应，并且依赖Saa的中性粒细胞迁移需要NF-κB依赖的基因表达。这些结果表明共生微生物群是调节全身中性粒细胞发育和功能多个方面的重要环境因素，并揭示了Saa-NF-κB信号轴在介导中性粒细胞迁移反应中的关键作用。
