This research explores how the cellular identity of dying cells influences the functional programming of macrophages during the clearing process. The study demonstrates that when macrophages ingest apoptotic neutrophils, they adopt a tissue-remodeling profile, whereas the consumption of apoptotic hepatocytes triggers an immunosuppressive state. These distinct immune signatures are further regulated by specific phagocytic receptors, such as AXL and MERTK, which are necessary for identifying certain types of dead cells. By utilizing a Schistosoma mansoni infection model, the authors show that selectively "feeding" macrophages specific apoptotic cells can significantly alter parasitic egg clearance and disease outcomes. Ultimately, the findings suggest that the origin of a dying cell serves as a critical instruction for immune diversification and potential cell-based therapies.

References:

• Imke Liebold et al. Apoptotic cell identity induces distinct functional responses to IL-4 in efferocytic macrophages.Science384,eabo7027(2024).DOI:10.1126/science.abo7027