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. Overall design: bone marrow-derived mouse macrophages treated with mast cell or mast cell trap supernatant for 3.5 hours