Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The dendritic cell (DC)-specific molecule DC-SIGN is a receptor for the HIV-1 envelope glycoprotein gp120 and is essential for the dissemination of HIV-1. DC-SIGN is expressed by DCs, both monocyte-derived DCs and DCs in several tissues, including mucosa and lymph nodes. To identify a DC-SIGN(+) DC in blood that may be involved in HIV-1 infection through blood, we have analyzed the expression of DC-SIGN in human blood cells. Here we describe the characterization of a subset of DCs in human blood, isolated from T-/NK-/B-cell-depleted peripheral blood mononuclear cells (PBMCs) on the basis of expression of DC-SIGN. This subset coexpresses CD14, CD16, and CD33 and is thus of myeloid origin. In contrast to CD14(+) monocytes, DC-SIGN(+) blood cells display a DC-like morphology and express markers of antigen-presenting cells, including CD1c, CD11b, CD11c, CD86, and high levels of major histocompatibility complex (MHC) class I and II molecules. This DC population differs from other described CD14(-) blood DC subsets. Functionally, DC-SIGN(+) blood DCs are able to stimulate proliferation of allogeneic T cells and can produce tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) upon activation with lipopolysaccharide (LPS). When they encounter HIV-1, low amounts of these blood DC-SIGN(+) DCs enhance infection of T lymphocytes in trans, whereas blood monocytes and CD14(-) blood DCs are not capable of transmitting HIV-1. Therefore DC-SIGN(+) blood DCs can be the first target for HIV-1 upon transmission via blood; they can capture minute amounts of HIV-1 through DC-SIGN and transfer HIV-1 to infect target T cells in trans.
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PMID:Subset of DC-SIGN(+) dendritic cells in human blood transmits HIV-1 to T lymphocytes. 1217

The human gastric pathogen Helicobacter pylori spontaneously switches lipopolysaccharide (LPS) Lewis (Le) antigens on and off (phase-variable expression), but the biological significance of this is unclear. Here, we report that Le+ H. pylori variants are able to bind to the C-type lectin DC-SIGN and present on gastric dendritic cells (DCs), and demonstrate that this interaction blocks T helper cell (Th)1 development. In contrast, Le- variants escape binding to DCs and induce a strong Th1 cell response. In addition, in gastric biopsies challenged ex vivo with Le+ variants that bind DC-SIGN, interleukin 6 production is decreased, indicative of increased immune suppression. Our data indicate a role for LPS phase variation and Le antigen expression by H. pylori in suppressing immune responses through DC-SIGN.
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PMID:Helicobacter pylori modulates the T helper cell 1/T helper cell 2 balance through phase-variable interaction between lipopolysaccharide and DC-SIGN. 1549 23

The role of DC-SIGN on human rectal mucosal dendritic cells is unknown. Using highly purified human rectal mucosal DC-SIGN+ cells and an ultrasensitive real-time reverse transcription-PCR assay to quantify virus binding, we found that HLA-DR+/DC-SIGN+ cells can bind and transfer more virus than the HLA-DR+/DC-SIGN- cells. Greater than 90% of the virus bound to total mucosal mononuclear cells (MMCs) was accounted for by the DC-SIGN+ cells, which comprise only 1 to 5% of total MMCs. Significantly, anti-DC-SIGN antibodies blocked 90% of the virus binding when more-physiologic amounts of virus inoculum were used. DC-SIGN expression in the rectal mucosa was significantly correlated with the interleukin-10 (IL-10)/IL-12 ratio (r = 0.58, P < 0.002; n = 26) among human immunodeficiency virus (HIV)-positive patients. Ex vivo and in vitro data implicate the role of IL-10 in upregulating DC-SIGN expression and downregulating expression of the costimulatory molecules CD80/CD86. Dendritic cells derived from monocytes (MDDCs) in the presence of IL-10 render the MDDCs less responsive to maturation stimuli, such as lipopolysaccharide and tumor necrosis factor alpha, and migration to the CCR7 ligand macrophage inflammatory protein 3beta. Thus, an increased IL-10 environment could render DC-SIGN(+) cells less immunostimulatory and migratory, thereby dampening an effective immune response. DC-SIGN and the IL-10/IL-12 axis may play significant roles in the mucosal transmission and pathogenesis of HIV type 1.
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PMID:Binding and transfer of human immunodeficiency virus by DC-SIGN+ cells in human rectal mucosa. 1582 91

Exposure to ultraviolet (UV) light induces immunosuppression. Different evidences indicate that this phenomenon is mainly a consequence of the effect of UV light on skin dendritic cells (DC). To investigate the cellular and molecular basis of this type of immunosuppression, we assessed in vitro the effect of solar-simulated UV radiation on the phenotypic and functional characteristics of human monocyte-derived DC and Langerhans-like DC. UV radiation induced a decreased expression of molecules involved in antigen capture as DC-SIGN and the mannose receptor. This effect was accompanied by a diminished endocytic capacity, an enhanced expression of molecules involved in antigen presentation such as major histocompatibility complex-II and CD86, and a significant increase in their capability to stimulate T cells. Furthermore, irradiated DC failed to acquire a full mature phenotype upon treatment with lipopolysaccharide. On the other hand, solar-simulated radiation induced the secretion of tumor necrosis factor-alpha and interleukin (IL)-10 by DC, but no IL-12. Interestingly, solar-simulated UV radiation also caused an altered migratory phenotype, with an increased expression of CXCR4, and a lack of induction of CCR7, thus correlating with a high chemotactic response to stromal cell-derived factor 1(SDF-1) (CXCL12), but not to secondary lymphoid tissue chemokine (SLC) (CCL21). These data indicate that solar-simulated UV radiation induces a defective maturation and an anomalous migratory phenotype of DC.
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PMID:Solar-simulated ultraviolet radiation induces abnormal maturation and defective chemotaxis of dendritic cells. 1609 45

The skin harbors two dendritic cell (DC) subsets, Langerhans cells (LC) and interstitial/dermal DC (IDDC), which traffic to lymph nodes after inflammation and ultraviolet stress. To demonstrate that monocytes may act as DC precursors for skin DC in postinflammatory recolonization, we generated LC and IDDC from monocytes by using cytokines related to the T helper cell type 2 environment [granulocyte macrophage-colony stimulating factor/transforming growth factor-beta/interleukin-13/tumor necrosis factor alpha (GM-CSF/TGF-beta/IL-13/TNF-alpha)]. In this study, skin DC [LC as Langerin/CD207(+) cells and IDDC as DC-specific intercellular adhesion molecule-grabbing nonintegrin (SIGN)/CD209(+) cells] displayed desynchronized programs along their differentiation, activation/maturation processes in response to stimuli characteristics of a proinflammatory context. First, we demonstrate that monocytes are able to diverge simultaneously along two distinct pathways toward Langerin(+)-LC-type DC and DC-SIGN(+)-IDDC. Second, as TGF-beta is known to antagonize the TNF-alpha-induced maturation process of DC, we showed that IDDC did not mature and acquired a low CC chemokine receptor 7 (CCR7) receptor expression even when stimulated with prolonged incubation with TNF-alpha. It is striking that the LC subset is able to express a high level of CCR7 expression and the maturation marker DC-lysosome-associated membrane protein (DC-LAMP). Third, mixed LC and IDDC subsets secrete IL-10 and IL-12 when stimulated by CD40 ligand and lipopolysaccharide (LPS) but not after prolonged incubation with TNF-alpha. In contrast, LPS was a better activator of IL-10 secretion than the CD40 ligand for GM-CSF/IL-4-generated DC and for GM-CSF/TGF-beta/IL-13-generated LC and IDDC populations. To summarize, the phenotypic/migratory maturation status of LC may be more easily enhanced by stimuli mimicking a proinflammatory situation, and IDDC are more resistant. Moreover, our culture system provided a means of studying cross-talk between two skin DC outside of their respective skin compartment.
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PMID:Mixed Langerhans cell and interstitial/dermal dendritic cell subsets emanating from monocytes in Th2-mediated inflammatory conditions respond differently to proinflammatory stimuli. 1661 58

C-reactive protein (CRP) is an acute phase reactant protein considered to be the prototypic marker for inflammation and its associated diseases. However, little is known about how CRP affects the immune system. In this study, we investigated the effect of CRP on dendritic cell (DC) differentiation, activation and biological functions. CD14+ monocytes were purified from PBMC and differentiated into DC in vitro. CRP (10 microg/mL) substantially down-regulated expression of DC-SIGN (CD209) and the costimulatory molecules CD40 and CD86 during DC differentiation. This inhibitory effect was more pronounced when CRP was added at the early stage (0-2 days) of DC differentiation. The inhibitory effect of CRP could be specifically blocked by an anti-CD32 Ab. In addition, CRP dramatically down-regulated expression of the antigen-uptake molecules CD205 and CD206, resulting in reduced DC endocytosis. Furthermore, CRP down-regulated expression of the costimulatory molecules CD40, CD80 and CD86 as well as the DC maturation marker CD83 after lipopolysaccharide-induced DC maturation. CRP-treated DC also showed an inhibitory effect on allogeneic T cell proliferation in a mixed leukocyte reaction. CRP treatment of activated DC preferentially decreased production of the proinflammatory and inflammatory cytokines IL-6, IL-8, IL-12, TNF-alpha, MIP-1alpha, MIP-1beta and MCP-1. This work reveals a new role for CRP in modulating the immune system by inhibiting DC differentiation, maturation and functions mainly through FcgammaRIIa/CD32.
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PMID:C-reactive protein impairs human CD14+ monocyte-derived dendritic cell differentiation, maturation and function. 1705 17

Contrasting observations raise the question of the role of mycobacterial derived products as compared with the whole bacterium Mycobacterium tuberculosis on maturation and function of human dendritic cells (DCs). DC-SIGN has been identified as the key DC receptor for M. tuberculosis through its interaction with the mannosylated lipoarabinomannan (ManLAM). Although ManLAM is a major mycobacterial component released from infected antigen-presenting cells, there is no formal evidence yet for an effect of ManLAM per se on DC maturation and function. DCs activated with purified ManLAM displayed an intermediate maturation phenotype as compared with lipopolysaccharide fully matured DCs with reduced expression of MHC class I and class II molecules, CD83 and CD86 and of the chemokine receptor CCR7. They were sensitive to autologous natural killer (NK) lysis, thus behaving like immature DCs. However, ManLAM-activated DCs lost phagocytic activity and triggered priming of naive T-cells, confirming their intermediate maturation. Partial maturation of ManLAM-activated DCs was overcome by triggering the CD40/CD40L pathway as a second signal, which completed maturation phenotypically and abolished autologous NK lysis susceptibility. Altogether, these data provide evidence that ManLAM may induce a partial maturation phenotype on non-infected bystander DCs during infection suggesting that ManLAM released from infected cells might impair adaptive immune response towards M. tuberculosis.
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PMID:Intermediate maturation of Mycobacterium tuberculosis LAM-activated human dendritic cells. 1725 79

Mycobacterium tuberculosis lipomannans (LMs) modulate the host innate immune response. The total fraction of Mycobacterium bovis BCG LM was shown both to induce macrophage activation and pro-inflammatory cytokines through Toll-like receptor 2 (TLR2) and to inhibit pro-inflammatory cytokine production by lipopolysaccharide (LPS)-activated macrophages through a TLR2-independent pathway. The pro-inflammatory activity was attributed to tri- and tetra-acylated forms of BCG LM but not the mono- and di-acylated ones. Here, we further characterize the negative activities of M. bovis BCG LM on primary murine macrophage activation. We show that di-acylated LMs exhibit a potent inhibitory effect on cytokine and NO secretion by LPS-activated macrophages. The inhibitory activity of mycobacterial mannose-capped lipoarabino-mannans on human phagocytes was previously attributed to their binding to the C-type lectins mannose receptor or specific intracellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN). However, we found that di-acylated LM inhibition of LPS-induced tumor necrosis factor secretion by murine macrophages was independent of TLR2, mannose receptor, or the murine ortholog SIGNR1. We further determined that tri-acyl-LM, an agonist of TLR2/TLR1, promoted interleukin-12 p40 and NO secretion through the adaptor proteins MyD88 and TIRAP, whereas the fraction containing tetra-acylated LM activated macrophages in a MyD88-dependent fashion, mostly through TLR4. TLR4-dependent pro-inflammatory activity was also seen with M. tuberculosis LM, composed mostly of tri-acylated LM, suggesting that acylation degree per se might not be sufficient to determine TLR2 versus TLR4 usage. Therefore, LM acylation pattern determines the anti-inflammatory versus pro-inflammatory effects of LM through different pattern recognition receptors or signaling pathways and may represent an additional mean of regulating the host innate immunity by mycobacteria.
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PMID:Acylation determines the toll-like receptor (TLR)-dependent positive versus TLR2-, mannose receptor-, and SIGNR1-independent negative regulation of pro-inflammatory cytokines by mycobacterial lipomannan. 1761 34

Bacillus anthracis secretes two bipartite toxins, edema toxin (ET) and lethal toxin (LT), which impair immune responses and contribute directly to the pathology associated with the disease anthrax. Edema factor, the catalytic subunit of ET, is an adenylate cyclase that impairs host defenses by raising cellular cyclic AMP (cAMP) levels. Synthetic cAMP analogues and compounds that raise intracellular cAMP levels lead to phenotypic and functional changes in dendritic cells (DCs). Here, we demonstrate that ET induces a maturation state in human monocyte-derived DCs (MDDCs) similar to that induced by lipopolysaccharide (LPS). ET treatment results in downregulation of DC-SIGN, a marker of immature DCs, and upregulation of DC maturation markers CD83 and CD86. Maturation of DCs by ET is accompanied by an increased ability to migrate toward the lymph node-homing chemokine macrophage inflammatory protein 3beta, like LPS-matured DCs. Interestingly, cotreating with LT differentially affects the ET-induced maturation of MDDCs while not inhibiting ET-induced migration. These findings reveal a mechanism by which ET impairs normal innate immune function and may explain the reported adjuvant effect of ET.
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PMID:Anthrax edema toxin induces maturation of dendritic cells and enhances chemotaxis towards macrophage inflammatory protein 3beta. 1927 56

In humans, Klebsiella pneumoniae is a saprophytic bacterium of the nasopharyngeal and intestinal mucosae that is also frequently responsible for severe nosocomial infections. Two major factors of virulence, capsular polysaccharide (CPS) and lipopolysaccharide (LPS) O antigen, are involved in mucosal colonization and the development of infections. These bacterial surface structures are likely to play major roles in interactions with the mucosal immune system, which are orchestrated by a network of surveillance based on dendritic cells (DCs). To determine the roles of K. pneumoniae CPS and LPS in the DC response, we investigated the response of immature human monocyte-derived DCs to bacterial challenge with a wild-type strain and its isogenic mutants deficient in CPS or LPS O-antigen production. As observed by flow cytometry and confocal laser microscopy, the rate of phagocytosis was inversely proportional to the amount of CPS on the bacterial cell surface, with LPS playing little or no role. The K. pneumoniae wild-type strain induced DC maturation with upregulation of CD83, CD86, and TLR4 and downregulation of CD14 and DC-SIGN. With CPS mutants, we observed a greater decrease in DC-SIGN, suggesting a superior maturation of DCs. In addition, incubation of DCs with CPS mutants, and to a lesser extent with LPS mutants, resulted in significantly higher Th1 cytokine production. Combined, our findings suggest that K. pneumoniae CPS, by hampering bacterial binding and internalization, induces a defective immunological host response, including maturation of DCs and pro-Th1 cytokine production, whereas the LPS O antigen seems to be involved essentially in DC activation.
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PMID:Roles of capsule and lipopolysaccharide O antigen in interactions of human monocyte-derived dendritic cells and Klebsiella pneumoniae. 1984 Oct 82


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