A nerve and mast cell sentinel system releases extracellular condensates to induce macrophage repair.
Salm L., Lopez MA., Jenkins E., Shim R., Tejada O., Abou Mehrem B., Huang S., Etemadi Nezhad P., Derakhshani A., Lee W-Y., Nusse Y., Mewburn JB., Noskovicova N., Bayer J., Rashid MU., Li X., Baltaci Z., Young D., Carneiro MB., Fritzsche M., Jakubzick CV., Peters NC., Deniset JF., Zindel J., Dufour A., Yipp BG., Ditlev JA., Dustin ML., Canton J., Kubes P.
There is a higher density of immune cells in peritoneal fluid than is found in blood. Thus, any perturbations, from sterile injury to endometriosis to ovarian cancer, require immune cells to recognize and nucleate to these sites. Using peritoneal injuries as a prototype, we saw a massive recruitment of large peritoneal macrophages (LPMs) interspersed with mast cells. The mast cells were activated by sensory neurons to mobilize their 1-μm granules to the cell surface. Lattice light sheet microscopy unveiled a new step in the mast cell degranulation. After granules fused with the plasma membrane, cytonemes (very thin long filopodia) grabbed the granules from the mast cell surface and deposited them on neighboring LPMs. The granules were membraneless biomolecular condensates and harbored more than 200 different proteins, including MARCO, which mediated rapid LPM aggregation to the injury nidus. The condensates also induced a repair-like phenotype in the macrophages that helped heal the injury site.