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• Endothelial cells express Tlr4 and Myd88 and, following in vivo LPS or E. coli stimulation, are the prime source of G-CSF. • Endothelial cells are sensors of systemically spread pathogens and subsequent drivers of bone marrow emergency granulopoiesis. For personal use only.on March 6, 2016. by guest www.bloodjournal.orgFrom 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 bone marrow stromal cells, are essential cells for this process. Indeed, ECs from multiple tissues including BM express high levels of Tlr4 and Myd88, and are th