TY - JOUR KW - Antigens, CD1 KW - Cell Adhesion Molecules KW - Cell Differentiation KW - Dendritic Cells KW - Gene Expression KW - Humans KW - Immunity, Innate KW - Lectins, C-Type KW - leprosy KW - Lymphocyte Activation KW - Macrophages KW - Membrane Glycoproteins KW - Monocytes KW - Receptors, Cell Surface KW - T-Lymphocytes KW - Toll-Like Receptors AU - Krutzik SR AU - Tan B AU - Li H AU - Ochoa MT AU - Liu PT AU - Sharfstein SE AU - Graeber T AU - Sieling PA AU - Liu Y AU - Rea T AU - Bloom B AU - Modlin RL AB -

Leprosy enables investigation of mechanisms by which the innate immune system contributes to host defense against infection, because in one form, the disease progresses, and in the other, the infection is limited. We report that Toll-like receptor (TLR) activation of human monocytes induces rapid differentiation into two distinct subsets: DC-SIGN+ CD16+ macrophages and CD1b+ DC-SIGN- dendritic cells. DC-SIGN+ phagocytic macrophages were expanded by TLR-mediated upregulation of interleukin (IL)-15 and IL-15 receptor. CD1b+ dendritic cells were expanded by TLR-mediated upregulation of granulocyte-macrophage colony-stimulating factor (GM-CSF) and its receptor, promoted T cell activation and secreted proinflammatory cytokines. Whereas DC-SIGN+ macrophages were detected in lesions and after TLR activation in all leprosy patients, CD1b+ dendritic cells were not detected in lesions or after TLR activation of peripheral monocytes in individuals with the progressive lepromatous form, except during reversal reactions in which bacilli were cleared by T helper type 1 (TH1) responses. In tuberculoid lepromatous lesions, DC-SIGN+ cells were positive for macrophage markers, but negative for dendritic cell markers. Thus, TLR-induced differentiation of monocytes into either macrophages or dendritic cells seems to crucially influence effective host defenses in human infectious disease.

BT - Nature medicine C1 - http://www.ncbi.nlm.nih.gov/pubmed/15880118?dopt=Abstract DA - 2005 Jun DO - 10.1038/nm1246 IS - 6 J2 - Nat. Med. LA - eng N2 -

Leprosy enables investigation of mechanisms by which the innate immune system contributes to host defense against infection, because in one form, the disease progresses, and in the other, the infection is limited. We report that Toll-like receptor (TLR) activation of human monocytes induces rapid differentiation into two distinct subsets: DC-SIGN+ CD16+ macrophages and CD1b+ DC-SIGN- dendritic cells. DC-SIGN+ phagocytic macrophages were expanded by TLR-mediated upregulation of interleukin (IL)-15 and IL-15 receptor. CD1b+ dendritic cells were expanded by TLR-mediated upregulation of granulocyte-macrophage colony-stimulating factor (GM-CSF) and its receptor, promoted T cell activation and secreted proinflammatory cytokines. Whereas DC-SIGN+ macrophages were detected in lesions and after TLR activation in all leprosy patients, CD1b+ dendritic cells were not detected in lesions or after TLR activation of peripheral monocytes in individuals with the progressive lepromatous form, except during reversal reactions in which bacilli were cleared by T helper type 1 (TH1) responses. In tuberculoid lepromatous lesions, DC-SIGN+ cells were positive for macrophage markers, but negative for dendritic cell markers. Thus, TLR-induced differentiation of monocytes into either macrophages or dendritic cells seems to crucially influence effective host defenses in human infectious disease.

PY - 2005 SP - 653 EP - 60 T2 - Nature medicine TI - TLR activation triggers the rapid differentiation of monocytes into macrophages and dendritic cells. UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1409736/pdf/nihms4867.pdf VL - 11 SN - 1078-8956 ER -