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Peripheral priming induces plastic transcriptomic and proteomic responses in circulating neutrophils required for pathogen containment

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Item Type:Article
Title:Peripheral priming induces plastic transcriptomic and proteomic responses in circulating neutrophils required for pathogen containment
Creators Name:Kaiser, R. and Gold, C. and Joppich, M. and Loew, Q. and Akhalkatsi, A. and Mueller, T.T. and Offensperger, F. and Droste Zu Senden, A. and Popp, O. and di Fina, L. and Knottenberg, V. and Martinez-Navarro, A. and Eivers, L. and Anjum, A. and Escaig, R. and Bruns, N. and Briem, E. and Dewender, R. and Muraly, A. and Akgöl, S. and Ferraro, B. and Hoeflinger, J.K.L. and Polewka, V. and Khaled, N.B. and Allgeier, J. and Tiedt, S. and Dichgans, M. and Engelmann, B. and Enard, W. and Mertins, P. and Hubner, N. and Weckbach, L. and Zimmer, R. and Massberg, S. and Stark, K. and Nicolai, L. and Pekayvaz, K.
Abstract: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 inflammation, resulting in functional shifts in vivo. Blocking de novo RNA synthesis in circulating neutrophils abrogates these plastic shifts and prevents the adaptation of antibacterial neutrophil programs by up-regulation of distinct effector molecules upon infection. These data underline transcriptional plasticity as a relevant mechanism of functional neutrophil reprogramming during acute infection to foster bacterial containment within the circulation.
Keywords:Gene Expression Profiling, Inflammation, Neutrophils, Proteomics, Transcriptome, Animals, Mice
Source:Science Advances
Publisher:American Association for the Advancement of Science
Page Range:eadl1710
Date:22 March 2024
Official Publication:https://doi.org/10.1126/sciadv.adl1710
PubMed:View item in PubMed

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