Neutrophil trapping and nexocytosis are mast cell processes for inflammatory signal relay

Neutrophils are sentinel immune cells with essential roles for our anti-microbial defense. Most of our knowledge on neutrophil trafficking and tissue navigation derived from models of sterile inflammation and infection. Here, we analyzed allergen-challenged mouse tissues and discovered that degranulating mast cells (MCs) trap living neutrophils inside them. MCs release the attractant leukotriene B4 to re-route neutrophils toward them, thus exploiting a chemotactic system which neutrophils normally use for intercellular communication. Neutrophils die as a consequence of mast cell intracellular trap (MIT) formation, but their undigested material remains stored inside MC vacuoles over days. MCs can use this debris to increase their functional and metabolic fitness. Additionally, they can also exocytose active neutrophilic compounds with a time delay (nexocytosis) and elicit a pro-inflammatory type 1 interferon response in surrounding macrophages. Together, our study highlights neutrophil trapping and nexocytosis as mast cell-dependent processes, which may relay neutrophilic features over the course of chronic allergic inflammation. bone marrow-derived mouse macrophages treated with mast cell or mast cell trap supernatant for 3.5 hours

中性粒细胞（Neutrophils）是一类免疫哨兵细胞，在机体抗微生物防御中发挥核心作用。目前学界对于中性粒细胞迁移与组织导航的认知，大多源自无菌炎症与感染模型的研究。本研究通过分析过敏原刺激后的小鼠组织，发现脱颗粒肥大细胞（mast cells, MCs）会将存活的中性粒细胞困于胞内。肥大细胞可释放趋化因子白三烯B4（leukotriene B4），将中性粒细胞重新招募至自身周围，借此利用中性粒细胞原本用于细胞间通讯的趋化系统。中性粒细胞会因肥大细胞胞内陷阱（mast cell intracellular trap, MIT）的形成而死亡，但它们未被消化的物质会在肥大细胞液泡中留存数日。肥大细胞可利用这些细胞碎片提升自身的功能与代谢适应性。此外，肥大细胞还可通过延迟胞吐（nexocytosis）释放具有活性的中性粒细胞源性物质，并触发周围巨噬细胞产生促炎型1型干扰素应答。综上，本研究证实中性粒细胞捕获与延迟胞吐是依赖于肥大细胞的过程，该过程可能在慢性过敏性炎症进程中传递中性粒细胞的功能特性。经肥大细胞或肥大细胞陷阱上清液处理3.5小时的骨髓源性小鼠巨噬细胞