02617nas a2200469   4500000000100000008004100001260001300042653001800055653002800073653002500101653002000126653002000146653001100166653002100177653002000198653001200218653002600230653001600256653002700272653001400299653002800313653001800341653002400359100001500383700001000398700000900408700001300417700001100430700001800441700001400459700001500473700001000488700001000498700001200508700001400520245010500534856007400639300001100713490000700724520140200731022001402133       2005                            d  c2005 Jun10aAntigens, CD110aCell Adhesion Molecules10aCell Differentiation10aDendritic Cells10aGene Expression10aHumans10aImmunity, Innate10aLectins, C-Type10aleprosy10aLymphocyte Activation10aMacrophages10aMembrane Glycoproteins10aMonocytes10aReceptors, Cell Surface10aT-Lymphocytes10aToll-Like Receptors1 aKrutzik SR1 aTan B1 aLi H1 aOchoa MT1 aLiu PT1 aSharfstein SE1 aGraeber T1 aSieling PA1 aLiu Y1 aRea T1 aBloom B1 aModlin RL00aTLR activation triggers the rapid differentiation of monocytes into macrophages and dendritic cells.  uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1409736/pdf/nihms4867.pdf  a653-600 v113 a<p>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.</p>  a1078-8956