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

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

  • Commun Biol. 2022 Aug 16;5(1):824. doi: 10.1038/s42003-022-03791-1.
Yan Yang 1,  Guoyu Liu 1,  Feng Li 1,  Lucas B Carey 2 3,  Changjin Sun 1,  Kaiping Ling 1,  Hiroyuki Tachikawa 4 5,  Morihisa Fujita 1 6,  Xiao-Dong Gao 7,  Hideki Nakanishi 8
Affiliations

Affiliations

  • 1 Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, 214122, China.
  • 2 Center for Quantitative Biology and Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.
  • 3 Ginkgo Bioworks, Boston, MA, 02210, USA.
  • 4 Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo, 113-8657, Japan.
  • 5 Collaborative Research Institute for Innovative Microbiology, University of Tokyo, Tokyo, 113-8657, Japan.
  • 6 Institute for Glyco-core Research (iGCORE), Gifu University, Gifu, 501-1193, Japan.
  • 7 Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, 214122, China. xdgao@jiangnan.edu.cn.
  • 8 Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, 214122, China. hideki@jiangnan.edu.cn.
PMID: 35974093 DOI: 10.1038/s42003-022-03791-1
Abstract

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.

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