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

Autor: Li K; Department of Biomedical Sciences, Division of Immunology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. zach.lee.2008@gmail.com.; F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. zach.lee.2008@gmail.com., Chatterjee A; Department of Biomedical Sciences, Division of Immunology, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Qian C; Department of Urology, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Lagree K; Department of Biomedical Sciences, Division of Immunology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Wang Y; Department of Biomedical Sciences, Division Cancer Biology and Therapeutics, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Becker CA; F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Freeman MR; Department of Urology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; Department of Biomedical Sciences, Division Cancer Biology and Therapeutics, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Murali R; Department of Biomedical Sciences, Division of Immunology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Yang W; Department of Biomedical Sciences, Division Cancer Biology and Therapeutics, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Underhill DM; Department of Biomedical Sciences, Division of Immunology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. David.Underhill@csmc.edu.; F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. David.Underhill@csmc.edu.; Department of Medicine, Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. David.Underhill@csmc.edu.
Jazyk: angličtina
Zdroj: Nature [Nature] 2024 Jun; Vol. 630 (8017), pp. 736-743. Date of Electronic Publication: 2024 Jun 05.
DOI: 10.1038/s41586-024-07499-6
Abstrakt: Phagocytosis is the process by which myeloid phagocytes bind to and internalize potentially dangerous microorganisms 1 . 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 features 2-8 . 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.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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