Antigen-presenting cells continually survey both healthy and diseased tissues, ingesting, processing and presenting antigens to T cells. Reporting in Nature, Krummel and colleagues uncover an unexpected new pathway by which macrophages sample cytosolic material from living cells, with important consequences for antigen processing and T cell priming.
To define the underlying mechanism, the authors used in vitro co-culture systems in which bone marrow-derived macrophages (BMDMs) were exposed to highly viable donor cells expressing cytosolic reporters. BMDM uptake of small amounts of fluorescent protein from donor cells required direct cell–cell contact and was only weakly dependent on soluble vesicles such as exosomes. Importantly, blocking caspase activation or monitoring apoptosis reporters revealed that sampling occurred predominantly from live, non-apoptotic cells, establishing that cell death is not a prerequisite for antigen acquisition.