Divergent granulopoiesis at extramedullary sites safeguards antibacterial host defense
Extramedullary organs such as the spleen can assume granulopoiesis as a supportive mechanism to cope with increased demands during persistent inflammation. However, the quantitative output of extramedullary granulopoiesis is limited, and whether the spleen provides neutrophils of a qualitative difference remains unclear. Here, we found that splenic stress granulopoiesis is associated with distinct neutrophil production and differentiation trajectories. Myeloid progenitors in the spleen engaged in accelerated production of neutrophils with an immature phenotype. Yet, neutrophils generated during persistent stress granulopoiesis were fully competent to exert antimicrobial functions and were necessary to contain bacterial invasion in the bladder. Activation of type I interferon signaling in the spleen was required for splenic neutrophil priming, and its loss impaired antibacterial host defense. Thus, the spleen provides an immunological environment for stress-induced rapid production and priming of highly active neutrophils to meet demands during infection.
Authors
- Mathis Richter (ORCID: https://orcid.org/0000-0002-3110-6137)
- Ulrich Kalinke (ORCID: https://orcid.org/0000-0003-0503-9564)
- Miguel Palomino‐Segura (ORCID: https://orcid.org/0000-0003-1614-1222)
- Stephan Ludwig (ORCID: https://orcid.org/0000-0003-4490-3052)
- Raphael Chevre (ORCID: https://orcid.org/0000-0002-7564-2919)
- Stefan Lienenklaus (ORCID: https://orcid.org/0000-0003-4790-3445)
- Carlos Silvestre-Roig (ORCID: https://orcid.org/0000-0003-1169-7475)
- Andrea Herrero-Cervera
- Collins Osei-Sarpong (ORCID: https://orcid.org/0000-0002-1093-5147)
- Quinte Braster
- Andrea Cerutti (ORCID: https://orcid.org/0000-0003-3026-4704)
- Yvonne Börgeling
- Jadwiga Jabłońska (ORCID: https://orcid.org/0000-0003-1490-2542)
- Claudia Tulotta (ORCID: https://orcid.org/0000-0002-4554-3709)
- Mauricio Guzmán (ORCID: https://orcid.org/0000-0002-4447-2064)
- Noelia Alonso-Gonzalez
- Rui Benedito (ORCID: https://orcid.org/0000-0003-2458-3055)
- Artur Kibler (ORCID: https://orcid.org/0000-0002-4723-4993)
- Frank Rosenbauer (ORCID: https://orcid.org/0000-0001-7977-9421)
- Ralf Zimmer (ORCID: https://orcid.org/0000-0003-1439-2327)
- David Ahern (ORCID: https://orcid.org/0000-0002-7006-7396)
- Petra Dersch (ORCID: https://orcid.org/0000-0001-8177-3280)
- Claudia Monaco (ORCID: https://orcid.org/0000-0003-1985-4914)
- Sara Noemi Reinartz Groba
- Andrés Hidalgo (ORCID: https://orcid.org/0000-0001-5513-555X)
- Triantafyllos Chavakis (ORCID: https://orcid.org/0000-0002-1869-5141)
- Jordi Sintes (ORCID: https://orcid.org/0000-0002-1836-7076)
- Patricia Lemnitzer
- Vincent Suerdieck
- Samriti Sharma
- Ali Hageb
- Merieme Farjia
- Eduardo Ortega
- Francisco J. Arenas Cerro (ORCID: https://orcid.org/0009-0000-5987-8828)
- Hannah Flueter (ORCID: https://orcid.org/0009-0001-8669-524X)
- Alexander Bender (ORCID: https://orcid.org/0009-0000-4295-5057)
- Oliver Soehnlein (ORCID: https://orcid.org/0009-0009-0944-2706)
- Lina M. Vöcking (ORCID: https://orcid.org/0009-0003-3323-1884)
- Daniel R. Engel (ORCID: https://orcid.org/0000-0001-7301-353X)
Institutions
- Institució Catalana de Recerca i Estudis Avançats (ES)
- University of Münster (DE)
- Spanish National Centre for Cardiovascular Research (ES)
- Yale University (US)
- Medizinische Hochschule Hannover (DE)
- Humboldt-Universität zu Berlin (DE)
- University of Oxford (GB)
- BioLegend (United States) (US)
- Essen University Hospital (DE)
- Helmholtz Centre for Infection Research (DE)
- Hospital Del Mar (ES)
- Leibniz-Institute for Food Systems Biology at the Technical University of Munich (DE)
- Roche (Spain) (ES)
- Center for Experimental and Clinical Infection Research (DE)
- Max Planck Institute for Molecular Biomedicine (DE)
- University of Duisburg-Essen (DE)
- Technische Universität Dresden (DE)
- Charité - Universitätsmedizin Berlin (DE)
- Universidad de Extremadura (ES)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Science Immunology
- Published
- 2026-04-17
- DOI
- https://doi.org/10.1126/sciimmunol.adw7077
- Primary Topic
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Kennedy Trust for Rheumatology Research
- British Heart Foundation
- Deutsche Forschungsgemeinschaft
- Fondation Leducq
- Ministerio de Ciencia y Tecnología
- European Research Council
- European Regional Development Fund