Temporal phosphoproteomic programmes set a redox-gated rheostat on neutrophil phagocytosis

Human neutrophils show a two-hour, S. aureus–driven phosphoproteomic switch where early phosphorylation programs drive uptake, while late windows suppress the kinome and de-activate phagocytic machinery.

• Why it matters: Neutrophils must balance bacterial killing with host tissue damage, but how prior encounters tune later phagocytosis is incompletely understood.
• What they did: The study profiled human neutrophil proteome and phosphoproteome across two hours of Staphylococcus aureus exposure with five functional readouts, then used KINETIC correlation plus a genome-wide CRISPR knockout screen in PLB-985 cells.
• The result: Late-window neutrophils exhibit impaired phagocytosis and phagosomal acidification on re-challenge; KEAP1 is the strongest phagocytic brake, and KEAP1 loss or NADPH oxidase inhibition partially rescues re-exposed phagocytosis.