Direct neutrophil and T cell contact with macrophages induces release of phagosomally processed PAMPs via eructophagy

Macrophages play a pivotal role in clearing debris and microbes from the microenvironment via phagocytosis and orchestrating local inflammation. Although pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) are understood to mostly be released through the synthesis and secretion of soluble mediators, such as cytokines and eicosanoids, it has been recently proposed that macrophages can release previously phagocytosed and processed PAMPs and DAMPs into the local microenvironment via a process termed eructophagy, and that these, in turn, can activate recently recruited leukocytes. Additionally, it has been commonly observed that local macrophages physically interact with other leukocytes, such as neutrophils and T cells, recruited to sites of inflammation. This study demonstrates that eructophagy in macrophages is significantly induced during physical interaction with neutrophils and T cells, which is mediated by ICAM1 on macrophages and lymphocyte function-associated antigen 1 (LFA1) on neutrophils and T cells. Notably, ICAM1 activation alone is sufficient to trigger eructophagy in macrophages and is dependent on Lyn kinase. Through this mechanism, it is proposed that neutrophils and lymphocytes can influence their own activation by interacting with local macrophages containing PAMP-containing phagolysosomes, which subsequently triggers PAMP release into the local microenvironment through eructophagy.