Systemic bacterial infection induces a hematopoietic response program termed 
"emergency granulopoiesis" that is characterized by increased de novo bone 
marrow (BM) neutrophil production. How loss of local immune control and 
bacterial dissemination is sensed and subsequently translated into the switch 
from steady-state to emergency granulopoiesis is, however, unknown. Using 
tissue-specific myeloid differentiation primary response gene 88 
(Myd88)-deficient mice and in vivo lipopolysaccharide (LPS) administration to 
model severe bacterial infection, we here show that endothelial cells (ECs) but 
not hematopoietic cells, hepatocytes, pericytes, or BM stromal cells, are 
essential cells for this process. Indeed, ECs from multiple tissues including BM 
express high levels of Tlr4 and Myd88 and are the primary source of granulocyte 
colony-stimulating factor (G-CSF), the key granulopoietic cytokine, after LPS 
challenge or infection with Escherichia coli. EC-intrinsic MYD88 signaling and 
subsequent G-CSF production by ECs is required for myeloid progenitor lineage 
skewing toward granulocyte-macrophage progenitors, increased colony-forming unit 
granulocyte activity in BM, and accelerated BM neutrophil generation after LPS 
stimulation. Thus, ECs catalyze the detection of systemic infection into 
demand-adapted granulopoiesis.