Model for pathogen sensing and subsequent translation into emergency granulopoiesis. (1) Gram-negative bacteria and/or their structural components that have gained access to the systemic circulation are recognized by TLR4-expressing endothelial cells (2), thereby indicating an emergency state. Upon TLR4/MYD88 signaling in endothelial cells, G-CSF is released in large quantities (3). In the bone marrow, endothelial cell–derived G-CSF acts on myeloid precursors expressing the G-CSF receptor resulting in enhanced generation, accelerated turnover, and increased neutrophil release from the bone marrow to the systemic circulation (4). These neutrophils are recruited to the site of infection (5) where they participate in clearing the pathogen (6).