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In response to severe bacterial infection, bone marrow hematopoietic activity shifts toward promoting granulopoiesis. The underlying cell signaling mechanisms remain obscure. To study the role of Toll-like receptor 4 (TLR4)/stem cell antigen-1 (Sca-1) signaling in this process, bacteremia was induced in mice by intravenous injection of Escherichia coli. A subgroup of animals also received intravenous 5-bromo-2-deoxyuridine (BrdU). In a separate set of experiments, bone marrow lineage-negative (lin⁻) stem cell growth factor receptor-positive (c-kit⁺) Sca-1⁻ cells containing primarily common myeloid progenitors were cultured in vitro without or with E. coli lipopolysaccharide (LPS). In genotypic background control mice, bacteremia significantly upregulated Sca-1 expression by lin⁻ c-kit⁺ cells, as reflected by a marked increase in BrdU-negative lin⁻ c-kit⁺ Sca-1⁺ cells in the bone marrow. In mice with the TLR4 gene …