biostudies-literatureUnknown10(12)Kaiser RNeutrophils rapidly respond to inflammation and infection, but to which degree their functional trajectories after mobilization from the bone marrow are shaped within the circulation remains vague. Experimental limitations have so far hampered neutrophil research in human disease. Here, using innovative fixation and single-cell-based toolsets, we profile human and murine neutrophil transcriptomes and proteomes during steady state and bacterial infection. We find that peripheral priming of circulating neutrophils leads to dynamic shifts dominated by conserved up-regulation of antimicrobial genes across neutrophil substates, facilitating pathogen containment. We show the TLR4/NF-κB signaling-dependent up-regulation of canonical neutrophil activation markers like CD177/NB-1 during acute inflaScience advanceseadl1710https://www.ebi.ac.uk/biostudies/studies/S-EPMC11093074biostudies-literaturePeripheral priming induces plastic transcriptomic and proteomic responses in circulating neutrophils required for pathogen containment.PMC11093074Anjum ATiedt SAkgol SStark KOffensperger FZimmer RKnottenberg VJoppich MHubner NGold CPolewka VPekayvaz KKaiser RPopp OBriem ENicolai LEivers LMuraly AAkhalkatsi AWeckbach LDroste Zu Senden AKhaled NBEngelmann BMassberg SEscaig RFerraro BDichgans MDewender REnard WBruns Ndi Fina LMueller TTHoeflinger JKLAllgeier JMartinez-Navarro ALoew QMertins PfalsePeripheral priming induces plastic transcriptomic and proteomic responses in circulating neutrophils required for pathogen containment.Neutrophils rapidly respond to inflammation and infection, but to which degree their functional trajectories after mobilization from the bone marrow are shaped within the circulation remains vague. Experimental limitations have so far hampered neutrophil research in human disease. Here, using innovative fixation and single-cell-based toolsets, we profile human and murine neutrophil transcriptomes and proteomes during steady state and bacterial infection. We find that peripheral priming of circulating neutrophils leads to dynamic shifts dominated by conserved up-regulation of antimicrobial genes across neutrophil substates, facilitating pathogen containment. We show the TLR4/NF-κB signaling-dependent up-regulation of canonical neutrophil activation markers like CD177/NB-1 during acute infla2024-01-01T00:00:00Z2024 Mar2026-06-01T11:56:00.831Z2026-04-08T12:02:18.623ZS-EPMC110930743851796810.1126/sciadv.adl1710