Phagocytes are immune cells that protect the body by engulfing and digesting bacteria, viruses, fungi, and dead or damaged cells. Macrophages, neutrophils, and dendritic cells are among the primary phagocytes. They are crucial in innate immunity—the body’s primary defense against infections. Phagocytes recognize, capture, and destroy pathogenic microorganisms.
When phagocytes detect a microbial threat, they activate innate immunity receptors, triggering an inflammatory response that attracts other immune cells to combat the infection. These innate immunity receptors recognize various proteins or sugars on the surface of microorganisms, activating multiple signaling pathways.
The process by which phagocytes engulf and digest microorganisms is called phagocytosis. Captured pathogenic microorganisms are enclosed in a phagosome—a vesicle inside the cell where they are destroyed using an acidic environment, enzymes, and reactive oxygen species. These processes ensure the pathogen’s destruction and prevent its spread in the body.
Scientists from Cedars-Sinai Medical Center in the USA developed a method to study the receptors and signaling pathways used by macrophages to recognize yeast. They hypothesized that studying proteins accumulating in phagosomes after yeast capture would help identify the receptors and mechanisms macrophages use to combat fungal infections.
Researchers used the enzyme APEX2 to label proteins engulfed by phagocytes and track them inside phagosomes. To do this, they engineered Saccharomyces cerevisiae yeast and bacteria expressing APEX2 on their surface and fed them to mouse bone marrow macrophages. Adding hydrogen peroxide triggered the labeling of proteins inside the phagosomes, which were then analyzed using mass spectrometry.
PD-L1 Accumulates During Yeast Phagocytosis
The protein composition in phagosomes changes depending on the ingested microorganism. After engulfing yeast, the protein PD-L1 accumulated in phagosomes, an unexpected finding. PD-L1 expression on phagocytes significantly increases under inflammatory conditions, suggesting that PD-L1 may play a crucial role in innate immune responses. Microscopy confirmed that PD-L1 surrounds yeast particles inside phagosomes, unlike phagosomes containing ingested bacteria.
PD-L1 Directly Interacts with Yeast
The scientists investigated whether the PD-L1 protein interacts with yeast in phagosomes. They extracted yeast from phagosomes and incubated them with PD-L1 and other proteins. The results showed that PD-L1 binds to yeast only after processing inside phagosomes. Fungi, like Candida, interact with PD-L1 similarly, which indicates that PD-L1 recognizes a specific ligand exposed when the yeast cell wall is broken down. This ligand was identified as the yeast protein Rpl20b. The interaction between PD-L1 and the yeast protein Rpl20b supports the antifungal response of macrophages, including the production of the cytokine IL-10.
Conclusion
The PD-L1 receptor binds to the yeast protein Rpl20b, triggering an immune response to fungal infections. This binding occurs only after yeast is processed in phagosomes, where the yeast cell wall is broken down, exposing the Rpl20b protein. The interaction between the yeast protein Rpl20b and the PD-L1 receptor stimulates the antifungal response of macrophages.
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Reference
Profiling phagosome proteins identifies PD-L1 as a fungal-binding receptor
