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

Area of Science:

• Immunology
• Cell Biology
• Microbiology

Background:

• Phagocytosis is a key innate immune process where myeloid cells engulf microorganisms.
• Phagosomes mature into hubs of immune signaling, processing microbial components.
• Understanding phagosomal protein dynamics is crucial for host-pathogen interactions.

Purpose of the Study:

• To develop a novel method for identifying proteins within phagosomes.
• To compare phagosomal content when interacting with distinct microorganisms.
• To uncover new host-microbe recognition mechanisms.

Main Methods:

• Proximity labeling of phagosomal contents (PhagoPL) was developed.
• Phagosomes containing model yeast and bacteria were analyzed.
• Surface display library screening identified protein ligands.

Main Results:

• PhagoPL successfully identified proteins localizing to phagosomes.
• Programmed death-ligand 1 (PD-L1) was unexpectedly enriched in yeast-containing phagosomes.
• PD-L1 was found to bind yeast directly, with Rpl20b identified as a fungal ligand.

Conclusions:

• PhagoPL is an effective tool for analyzing phagosomal protein composition.
• PD-L1 acts as a specific receptor for fungal components within phagosomes.
• This interaction influences cytokine production, highlighting a novel immune regulatory pathway.