Macrophages, T cells and neutrophils work together in the immune system, with macrophages clearing pathogens and debris while signalling neutrophils and T cells to regulate immune responses. Eructophagy is a process in which macrophages amplify local inflammation by releasing processed pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) into the microenvironment. Here (Nguyen et al., 2025), Robin Yates and colleagues show that eructophagy is amplified through the direct engagement of intercellular adhesion molecule 1 (ICAM1) on macrophages with lymphocyte function-associated antigen 1 (LFA1) on neutrophils and T cells. Notably, coculturing macrophages with either neutrophils or T cells while blocking ICAM1–LFA1 interactions – either genetically or with antibodies – prevents eructophagy, inhibiting PAMP release and subsequent T cell activation. Furthermore, the authors show that crosslinking macrophage ICAM1 alone is sufficient to trigger eructophagy, highlighting the direct engagement of this adhesion molecule as a crucial regulatory mechanism. In addition, macrophages containing experimental beads coated with T cell activators can activate both adjacent and nearby T cells. This finding suggests that lymphocytes can induce their own activation by engaging macrophage ICAM1, prompting the release of PAMPs that subsequently activate surrounding immune cells. Together, this work expands our understanding of immune cell interactions at sites of inflammation and adds a novel layer of immune communication.
