美国西达-西奈医疗中心David M. Underhill等研究人员合作发现，吞噬体蛋白质分析发现PD-L1是一种真菌结合受体。相关论文于2024年6月5日在线发表在《自然》杂志上。

研究人员开发了吞噬体内容物近距离标记（PhagoPL）技术，以鉴定定位在含有模型酵母和细菌的吞噬体中的蛋白质。通过比较含有不同演化和生化微生物的吞噬体蛋白质组成，研究人员意外地发现程序性死亡配体1（PD-L1）是一种，特异性富集在含有酵母的吞噬体中的蛋白质。研究人员发现，PD-L1在吞噬体中处理后会直接与酵母结合。通过表面展示文库筛选，研究人员发现核糖体蛋白Rpl20b是PD-L1的真菌蛋白配体。

利用生长素诱导的耗竭系统，研究人员发现巨噬细胞检测到Rpl20b会交叉调节不同细胞因子的产生，包括激活其他先天性免疫受体诱导的白细胞介素-10（IL-10）。因此，这项研究将PhagoPL确立为一种有用的方法，可用于量化宿主与微生物相互作用过程中富集在吞噬体中的蛋白质集合，例如将PD-L1鉴定为与真菌结合的受体。

据了解，吞噬是髓吞噬细胞与潜在危险微生物结合并将其内化的过程。在吞噬过程中，先天性免疫受体和相关信号蛋白被定位到成熟的吞噬体区，形成一个充满微生物感应功能的免疫信息处理中枢。

附：英文原文

Title: Profiling phagosome proteins identifies PD-L1 as a fungal-binding receptor

Author: Li, Kai, Chatterjee, Avradip, Qian, Chen, Lagree, Katherine, Wang, Yang, Becker, Courtney A., Freeman, Michael R., Murali, Ramachandran, Yang, Wei, Underhill, David M.

Issue&Volume: 2024-06-05

Abstract: Phagocytosis is the process by which myeloid phagocytes bind to and internalize potentially dangerous microorganisms1. During phagocytosis, innate immune receptors and associated signalling proteins are localized to the maturing phagosome compartment, forming an immune information processing hub brimming with microorganism-sensing features2,3,4,5,6,7,8. Here we developed proximity labelling of phagosomal contents (PhagoPL) to identify proteins localizing to phagosomes containing model yeast and bacteria. By comparing the protein composition of phagosomes containing evolutionarily and biochemically distinct microorganisms, we unexpectedly identified programmed death-ligand 1 (PD-L1) as a protein that specifically enriches in phagosomes containing yeast. We found that PD-L1 directly binds to yeast upon processing in phagosomes. By surface display library screening, we identified the ribosomal protein Rpl20b as a fungal protein ligand for PD-L1. Using an auxin-inducible depletion system, we found that detection of Rpl20b by macrophages cross-regulates production of distinct cytokines including interleukin-10 (IL-10) induced by the activation of other innate immune receptors. Thus, this study establishes PhagoPL as a useful approach to quantifying the collection of proteins enriched in phagosomes during host–microorganism interactions, exemplified by identifying PD-L1 as a receptor that binds to fungi.

DOI: 10.1038/s41586-024-07499-6

Source: https://www.nature.com/articles/s41586-024-07499-6