Lipopolysaccharide can block the potential of monocytes to differentiate into dendritic cells

Abstract: We examined whether priming mono-cytes (MO) with lipopolysaccharide (LPS) influ-enced their further differentiation into either mac-rophages (Mf) or dendritic cells (DC). LPS-primed MO differentiated into Mf when cultured further with Mf colony-stimulating factor (M-CSF) but, if cultured then with granulocyte/Mf (GM)-CSF and IL-4 (interleukin-4), only about 30 % of the cells differentiated into CD1a1CD142 DC and half be-came CD1a2CD141 Mf. Cytokines present during LPS priming could affect subsequent MO differen-tiation. Relative to priming with LPS alone, adding M-CSF to LPS did not modify differentiation of MO to Mf in further culture with M-CSF, nor did it change the way of differentiation of MO into DC was altered if culture was later switched to GM-CSF/ IL-4. Using GM-CSF/IL-4 plus LPS upon priming did not modify differentiation of MO to Mf in further culture with M-CSF, as compared to prim-ing with GM-CSF/IL-4 alone, but it counteracted the effect of LPS on the differentiation of MO to DC in further culture with GM-CSF/IL-4: about 75 % of cells then became DC. Alternatively, despite activa-tion by LPS, mature M-CSF-induced Mf preserved the potential to differentiate into DC on subsequent culture with GM-CSF/IL-4. Thus, LPS, a bacterial product known to sustain maturation of MO/Mf as well as of DC, may block the differentiation of MO into DC, except if signal triggering DC differentia-tion is delivered concomitantly, and modulate in this manner the induction of adaptive immune responses to infection. J. Leukoc. Biol. 65: 232