ORCID: https://orcid.org/0000-0003-1750-3395; Gold, Christoph ORCID: https://orcid.org/0009-0008-8994-1021; Joppich, Markus ORCID: https://orcid.org/0000-0002-6665-8951; Loew, Quentin; Akhalkatsi, Anastassia; Mueller, Tonina T. ORCID: https://orcid.org/0000-0002-3123-3064; Offensperger, Felix; Droste zu Senden, Augustin; Popp, Oliver ORCID: https://orcid.org/0000-0001-6240-4666; Fina, Lea di; Knottenberg, Viktoria; Martinez-Navarro, Alejandro ORCID: https://orcid.org/0000-0003-3893-1719; Eivers, Luke ORCID: https://orcid.org/0000-0002-6049-0377; Anjum, Afra ORCID: https://orcid.org/0000-0002-1976-4102; Escaig, Raphael; Bruns, Nils; Briem, Eva ORCID: https://orcid.org/0009-0003-7506-3882; Dewender, Robin ORCID: https://orcid.org/0009-0003-1192-3791; Muraly, Abhinaya ORCID: https://orcid.org/0000-0003-2114-7696; Akgöl, Sezer ORCID: https://orcid.org/0000-0002-3154-3214; Ferraro, Bartolo ORCID: https://orcid.org/0000-0003-3340-5605; Hoeflinger, Jonathan K. L. ORCID: https://orcid.org/0000-0002-8823-2177; Polewka, Vivien; Khaled, Najib Ben ORCID: https://orcid.org/0000-0002-9681-2542; Allgeier, Julian ORCID: https://orcid.org/0000-0001-7536-5715; Tiedt, Steffen ORCID: https://orcid.org/0000-0002-8817-8457; Dichgans, Martin ORCID: https://orcid.org/0000-0002-0654-387X; Engelmann, Bernd; Enard, Wolfgang ORCID: https://orcid.org/0000-0002-4056-0550; Mertins, Philipp ORCID: https://orcid.org/0000-0002-2245-528X; Hubner, Norbert ORCID: https://orcid.org/0000-0002-1218-6223; Weckbach, Ludwig ORCID: https://orcid.org/0000-0002-0981-2246; Zimmer, Ralf; Massberg, Steffen ORCID: https://orcid.org/0000-0001-7387-3986; Stark, Konstantin ORCID: https://orcid.org/0000-0002-5369-8399; Nicolai, Leo ORCID: https://orcid.org/0000-0003-0776-5885 and Pekayvaz, Kami ORCID: https://orcid.org/0000-0003-4040-650X
(2024):
Peripheral priming induces plastic transcriptomic and proteomic responses in circulating neutrophils required for pathogen containment.
In: Science Advances, Vol. 10, No. 12, eadl1710
[PDF, 22MB]
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.
| Item Type: | Journal article |
|---|---|
| EU Funded Grant Agreement Number: | 833440 |
| EU Projects: | Horizon 2020 > ERC Grants > ERC Advanced Grant > ERC Grant 833440: IMMUNOTHROMBOSIS - Cross-talk between platelets and immunity - implications for host homeostasis and defense |
| Faculties: | Biology Medicine > Institute for Stroke and Dementia Research (ISD) Medicine > Medical Center of the University of Munich > Medical Clinic and Outpatient Clinic I (Cardiology) |
| Subjects: | 500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine and health |
| URN: | urn:nbn:de:bvb:19-epub-116926-8 |
| ISSN: | 2375-2548 |
| Language: | English |
| Item ID: | 116926 |
| Date Deposited: | 05. Jun 2024, 05:51 |
| Last Modified: | 05. Jun 2024, 05:51 |
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