By using tissue-specific TLR pathway component myeloid differentiation primary response 88 (Myd88)-deficient mice, a recent study revealed that EC, not hematopoietic cells, hepatocytes, pericytes, or bone marrow (BM) stromal cells, are the primary source of granulocyte colony-stimulating factor (G-CSF) production in response to lipopolysaccharide (LPS) stimulation (15) or infection with Escherichia coli (E. coli), which mediated by the EC-intrinsic TLR4/Myd88 signaling pathway (16). Here, CSF3 is linked to infection.