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.