Carlos Silvestre-Roig, Raphael Chevre, Merieme Farjia, Alexander Bender, Lina M. Vöcking, Mathis Richter, Ali Hageb, Vincent Suerdieck, Francisco J. Arenas Cerro, Quinte Braster, Mauricio Guzmán, Jordi Sintes, Samriti Sharma, Patricia Lemnitzer, Claudia Tulotta, Yvonne Börgeling, Andrea Herrero-Cervera, Hannah Flueter, Sara Noemi Reinartz Groba, David Ahern, Collins Osei-Sarpong, Ralf Zimmer, Noelia Alonso-Gonzalez, Eduardo Ortega, Stefan Lienenklaus, Ulrich Kalinke, Stephan Ludwig, Daniel R. Engel, Frank Rosenbauer, Claudia Monaco, Petra Dersch, Artur Kibler, Andrea Cerutti, Triantafyllos Chavakis, Rui Benedito, Andrés Hidalgo, Jadwiga Jabłońska, Miguel Palomino‐Segura, Oliver Soehnlein
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.