Receptor for advanced glycation end-products (RAGE) mediates phagocytosis in nonprofessional phagocytes

The multiligand receptor RAGE (receptor for advanced glycation end-products) mediates phagocytosis in non-professional phagocytes (NPPs), for example through the use of RNA fragments as ligands for internalization. In mammals, both professional phagocytes and nonprofessional phagocytes (NPPs) can perform phagocytosis. However, limited targets are phagocytosed by NPPs, and thus, the mechanism remains unclear. We find that spores of the yeast Saccharomyces cerevisiae are internalized efficiently by NPPs. Analyses of this phenomenon reveals that RNA fragments derived from cytosolic RNA species are attached to the spore wall, and these fragments serve as ligands to induce spore internalization. Furthermore, we show that a multiligand receptor, RAGE (receptor for advanced glycation end-products), mediates phagocytosis in NPPs. RAGE-mediated phagocytosis is not uniquely induced by spores but is an intrinsic mechanism by which NPPs internalize macromolecules containing RAGE ligands. In fact, artificial particles labeled with polynucleotides, HMGB1, or histone (but not bovine serum albumin) are internalized in NPPs. Our findings provide insight into the molecular basis of phagocytosis by NPPs, a process by which a variety of macromolecules are targeted for internalization.

Automated summary

The multiligand receptor RAGE plays a crucial role in mediating phagocytosis by non-professional phagocytes (NPPs) through the use of RNA fragments as ligands for internalization. This study reveals a new mechanism of phagocytosis by NPPs, showing that spores of Saccharomyces cerevisiae are efficiently internalized by NPPs due to the attachment of RNA fragments derived from cytosolic RNA species to the spore wall. Furthermore, the researchers demonstrate that RAGE is involved in phagocytosis by NPPs, not only in response to spores but also to other macromolecules containing RAGE ligands.