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Pattern of cytokine responses to gram-positive and gram-negative commensal bacteria is profoundly changed when monocytes differentiate into dendritic cells

Journal article
Authors Helen Karlsson
Pia Larsson
Agnes E Wold
Anna Rudin
Published in Infect Immun
Volume 72
Issue 5
Pages 2671-8
Publication year 2004
Published at Institute of Internal Medicine, Dept of Rheumatology and Inflammation Research
Institute of Laboratory Medicine, Dept of Clinical Bacteriology
Institute of Internal Medicine
Pages 2671-8
Language en
Keywords Antigen Presentation, Antigens, CD14/metabolism, Cell Differentiation, Cytokines/*biosynthesis, Dendritic Cells/cytology/*immunology, Digestive System/immunology/microbiology, Gram-Negative Bacteria/*immunology, Gram-Positive Bacteria/*immunology, Humans, Immunity, Mucosal, Interleukin-10/biosynthesis, Interleukin-12/biosynthesis, Interleukin-6/biosynthesis, Membrane Glycoproteins/metabolism, Monocytes/cytology/*immunology, Phagocytosis, Protein Subunits/biosynthesis, Receptors, Cell Surface/metabolism, Toll-Like Receptor 2, Toll-Like Receptor 4, Toll-Like Receptors, Tumor Necrosis Factor-alpha/biosynthesis
Subject categories Immunobiology


The normal gastrointestinal bacterial flora is crucial for the maturation of acquired immunity via effects on antigen-presenting cells (APCs). Here we investigated how two types of APCs, monocytes and dendritic cells (DCs), react to different bacterial strains typical of the commensal intestinal microflora. Purified human 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 interleukin 12p70 (IL-12p70) and tumor necrosis factor (TNF), as detected by an enzyme-linked immunosorbent assay, in response to L. plantarum than in response to E. coli and V. parvula. In contrast, DCs secreted large 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 a response to the gram-positive strains correlated with lower surface expression of Toll-like receptor 2 (TLR2) on DCs than on monocytes. The surface expression of TLR4 on DCs was undetectable when it was analyzed by flow cytometry, but blocking this receptor decreased the TNF production in response to V. parvula, indicating that TLR4 is expressed at a low density on DCs. Gamma interferon increased the expression of TLR4 on DCs and also potentiated the cytokine response to the gram-negative strains. Our results indicate that when monocytes differentiate into DCs, their ability to respond to different commensal bacteria dramatically changes, and they become unresponsive to probiotic gram-positive bacteria. These results may have important implications for the abilities of different groups of commensal bacteria to regulate mucosal and systemic immunity.

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