Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, 214122, China.
Center for Quantitative Biology and Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.
Commun Biol. 2022 Aug 16;5(1):824. doi: 10.1038/s42003-022-03791-1.
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.
在哺乳动物中，专业吞噬细胞和非专业吞噬细胞（NPPs）都可以进行吞噬作用。然而，NPPs 吞噬的靶标有限，其机制尚不清楚。我们发现酵母酿酒酵母的孢子可以被 NPPs 有效内化。对这一现象的分析表明，细胞质 RNA 种类衍生的 RNA 片段附着在孢子壁上，这些片段作为配体诱导孢子内化。此外，我们表明，多配体受体 RAGE（晚期糖基化终产物受体）介导 NPP 中的吞噬作用。RAGE 介导的吞噬作用不是唯一由孢子诱导的，而是 NPPs 内化含有 RAGE 配体的大分子的内在机制。事实上，用多核苷酸、HMGB1 或组蛋白（而不是牛血清白蛋白）标记的人工颗粒被 NPPs 内化。我们的发现为 NPPs 吞噬作用的分子基础提供了深入了解，这是一种将各种大分子靶向内化的过程。
