Pattern of Cytokine Responses to Gram‐Positive and Gram‐Negative Commensal Bacteria is Profoundly Changed when Monocytes Differentiate into Dendritic Cells

Karlsson, H.; Larsson, P.; Wold, A. E.; Rudin, A.

The normal gastrointestinal flora is crucial for the maturation of the acquired immunity via effects on antigen‐presenting cells (APCs). Here, we have investigated how two types of APCs, monocytes and dendritic cells (DCs), react to different bacterial strains typical of the commensal intestinal flora. Purified monocytes and monocyte‐derived DCs were stimulated with UV‐inactivated gram‐positive (Lactobacillus plantarum and Bifidobacterium adolescentis) and gram‐negative (Escherichia coli and Veillonella parvula) bacterial strains. Monocytes produced higher levels of IL‐12p70 and TNF, as detected by ELISA, in response to L. plantarum than to E. coli and V. parvula. In contrast, DCs secreted high amounts of IL‐12p70, TNF, IL‐6 and IL‐10 in response to E. coli and V. parvula but were practically unresponsive to L. plantarum and B. adolescentis. The lack of response to the gram‐positive strains correlated with a lower surface expression of Toll‐like reseptor 2 (TLR2) on DCs compared to monocytes. The surface expression of TLR4 on DCs was undetectable when analysed by flow cytometry, but blocking this receptor decreased the TNF production in response to V. parvula, indicating that low TLR4 expression on DCs is sufficient to mount an inflammatory response to gram‐negative bacteria. IFN‐γ increased the expression of TLR4 on DCs and also potentiated the cytokine response to gram‐negative bacteria. Our results indicate that, when monocytes differentiate into DCs, their ability to respond to different commensal bacteria dramatically changes, thereby becoming unresponsive to probiotic gram‐positive bacteria. These results may have important implications for the capacity of different groups of commensal bacteria to regulate mucosal and systemic immunity.