Bacteria/CpG DNA down-modulates colony stimulating factor-1 receptor surface expression on murine bone marrow-derived macrophages with concomitant growth arrest and factor-independent survival

Unmethylated CpG motifs within bacterial DNA constitute a pathogen-associat ed molecular pattern recognized by the innate immune system. Many of the im munomodulatory functions of bacterial DNA can be ascribed to the ability to activate macrophages and dendritic cells. Here we show stimulatory DNA, li ke LPS, caused growth arrest of murine bone marrow-derived macrophages prol iferating in CSF-1, Stimulatory DNA caused selective down-modulation of CSF -1 receptor surface expression. Flow cytometric analysis of CSF-1-deprived bone marrow-derived macrophages revealed that in contrast to the synchronou s reduction of CSF-1 receptor upon CSF-1 addition, activating DNA (both bac terial DNA and CpG-containing oligonucleotide) caused rapid removal of rece ptor from individual cells leading to a bimodal distribution of surface exp ression at intermediate times or submaximal doses of stimulus. Despite caus ing growth arrest, both stimulatory DNA and LPS promoted factor-independent survival of bone marrow-derived macrophages, which was associated with pho sphorylation of the mitogen-activated protein kinase family members, extrac ellular-regulated kinase 1 and 2, CSF-1 receptor down-modulation may polari ze the professional APC compartment to the more immunostimulatory dendritic cell-like phenotype by suppressing terminal macrophage differentiation med iated by CSF-1.