scholarly journals Dendritic Cells Phagocytose and Are Activated byTreponema pallidum

2001 ◽  
Vol 69 (1) ◽  
pp. 518-528 ◽  
Author(s):  
Deborah A. Bouis ◽  
Taissia G. Popova ◽  
Akira Takashima ◽  
Michael V. Norgard
Keyword(s):  
Dendritic Cells ◽  
Cell Activation ◽  
Immune Cell ◽  
Transmitted Disease ◽  
Treponema Pallidum ◽  
Clinical Manifestations ◽  
Surface Expression ◽  
Interleukin 12 ◽  
Necrosis Factor Alpha ◽  
Dc Line

ABSTRACT Cell-mediated immune processes play a prominent role in the clinical manifestations of syphilis, a sexually transmitted disease of humans caused by spirochetal bacterium Treponema pallidum. The immune cell type that initiates the early immune response toT. pallidum thus far has not been identified. However, dendritic cells (DCs) are the first immune-competent cells to encounter antigens within skin or mucous membranes, the principal sites of early syphilitic infection. In the present study, immature DC line XS52, derived from murine skin, was utilized to examine T. pallidum-DC interactions and subsequent DC activation (maturation). Electron microscopy revealed that T. pallidumwas engulfed by DCs via both coiling and conventional phagocytosis and was delivered to membrane-bound vacuoles. The XS52 DC line expressed surface CD14 and mRNA for Toll-like receptors 2 and 4, molecules comprising important signaling components for immune cell activation by bacterial modulins. Both T. pallidum and a synthetic lipopeptide (corresponding to the 47-kDa major membrane lipoprotein) activated the XS52 DC line, as indicated by the secretion of interleukin-12 (IL-12), IL-1β, tumor necrosis factor alpha, and IL-6 and elevated surface expression of CD54. The combined data support the contention that DCs stimulated by T. pallidum and/or its proinflammatory membrane lipoproteins are involved in driving the cellular immune processes that typify syphilis.

scholarly journals CD4+ CD25+ Foxp3+ Regulatory T Cells, Dendritic Cells, and Circulating Cytokines in Uncomplicated Malaria: Do Different Parasite Species Elicit Similar Host Responses?

2010 ◽  
Vol 78 (11) ◽  
pp. 4763-4772 ◽  
Author(s):  
Raquel M. Gonçalves ◽  
Karina C. Salmazi ◽  
Bianca A. N. Santos ◽  
Melissa S. Bastos ◽  
Sandra C. Rocha ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Parasite Species ◽  
Inflammatory Responses ◽  
Clinical Symptoms ◽  
Clinical Manifestations ◽  
Surface Expression ◽  
Interleukin 10 ◽  
Treg Cells ◽  
Experimental Models ◽  
Necrosis Factor Alpha

ABSTRACT Clearing blood-stage malaria parasites without inducing major host pathology requires a finely tuned balance between pro- and anti-inflammatory responses. The interplay between regulatory T (Treg) cells and dendritic cells (DCs) is one of the key determinants of this balance. Although experimental models have revealed various patterns of Treg cell expansion, DC maturation, and cytokine production according to the infecting malaria parasite species, no studies have compared all of these parameters in human infections with Plasmodium falciparum and P. vivax in the same setting of endemicity. Here we show that during uncomplicated acute malaria, both species induced a significant expansion of CD4+ CD25+ Foxp3+ Treg cells expressing the key immunomodulatory molecule CTLA-4 and a significant increase in the proportion of DCs that were plasmacytoid (CD123+), with a decrease in the myeloid/plasmacytoid DC ratio. These changes were proportional to parasite loads but correlated neither with the intensity of clinical symptoms nor with circulating cytokine levels. One-third of P. vivax-infected patients, but no P. falciparum-infected subjects, showed impaired maturation of circulating DCs, with low surface expression of CD86. Although vivax malaria patients overall had a less inflammatory cytokine response, with a higher interleukin-10 (IL-10)/tumor necrosis factor alpha (TNF-α) ratio, this finding did not translate to milder clinical manifestations than those of falciparum malaria patients. We discuss the potential implications of these findings for species-specific pathogenesis and long-lasting protective immunity to malaria.

Morin Promotes the Production of Th2 Cytokine by Modulating Bone Marrow-Derived Dendritic Cells

2006 ◽  
Vol 34 (04) ◽  
pp. 667-684 ◽  
Author(s):  
Chia-Yang Li ◽  
Jau-Ling Suen ◽  
Bor-Luen Chiang ◽  
Pei-Dawn Lee Chao ◽  
Shih-Hua Fang
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Dendritic Cells ◽  
Interleukin 12 ◽  
Th2 Response ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Th Differentiation ◽  
Th1 And Th2 Responses

Our previous studies had reported that morin decreased the interleukin-12 (IL-12) and tumor necrosis factor-alpha (TNF-α) production in lipopolysaccharide (LPS)-activated macrophages, suggesting that morin may promote helper T type 2 (Th2) response in vivo. Dendritic cells (DCs) are the most potent antigen presenting cells and known to play a major role in the differentiation of helper T type 1 (Th1) and Th2 responses. This study aimed to reveal whether morin is able to control the Th differentiation through modulating the maturation and functions of DCs. Bone marrow-derived dendritic cells (BM-DCs) were incubated with various concentrations of morin and their characteristics were studied. The results indicated that morin significantly affects the phenotype and cytokine expression of BM-DCs. Morin reduced the production of IL-12 and TNF-α in BM-DCs, in response to LPS stimulation. In addition, the proliferative response of stimulated alloreactive T cells was significantly decreased by morin in BM-DCs. Furthermore, allogeneic T cells secreted higher IL-4 and lower IFN-γ in response to morin in BM-DCs. In conclusion, these results suggested that morin favors Th2 cell differentiation through modulating the maturation and function of BM-DCs.

scholarly journals Immunomodulatory Effects of Polysaccharide from Marine FungusPhoma herbarumYS4108 on T Cells and Dendritic Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Song Chen ◽  
Ran Ding ◽  
Yan Zhou ◽  
Xian Zhang ◽  
Rui Zhu ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Interleukin 12 ◽  
Related Factors ◽  
Knock Out ◽  
Specific Immunity

YCP, as a kind of natural polysaccharides from the mycelium of marine filamentous fungusPhoma herbarumYS4108, has great antitumor potentialviaenhancement of host immune response, but little is known about the molecular mechanisms. In the present study, we mainly focused on the effects and mechanisms of YCP on the specific immunity mediated by dendritic cells (DCs) and T cells. T cell /DC activation-related factors including interferon- (IFN-)γ, interleukin-12 (IL-12), and IL-4 were examined with ELISA. Receptor knock-out mice and fluorescence-activated cell sorting are used to analyze the YCP-binding receptor of T cells and DCs. RT-PCR is utilized to measure MAGE-A3 for analyzing the tumor-specific killing effect. In our study, we demonstrated YCP can provide the second signal for T cell activation, proliferation, and IFN-γproduction through binding to toll-like receptor- (TLR-) 2 and TLR-4. YCP could effectively promote IL-12 secretion and expression of markers (CD80, CD86, and MHC II)viaTLR-4 on DCs. Antigen-specific immunity against mouse melanoma cells was strengthened through the activation of T cells and the enhancement of capacity of DCs by YCP. The data supported that YCP can exhibit specific immunomodulatory capacity mediated by T cells and DCs.

scholarly journals Carrot Pomace Polysaccharide (CPP) Improves Influenza Vaccine Efficacy in Immunosuppressed Mice via Dendritic Cell Activation

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2740
Author(s):  
Pureum Sun ◽  
Yeeun Kim ◽  
Hoyoung Lee ◽  
Jihyun Kim ◽  
Bok Kyung Han ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Influenza Vaccine ◽  
Cell Activation ◽  
Cell Function ◽  
Immune Cell ◽  
Ex Vivo ◽  
The Elderly ◽  
Influenza Viruses ◽  
Health Concern ◽  
Dendritic Cell Activation

Despite the advancements in vaccination research and practices, influenza viruses remain a global health concern. Inducing a robust immune response by vaccination is especially challenging in the elderly, the immunocompromised, and persons with chronic illnesses. Polysaccharides derived from food may act as a safe and readily accessible means to boost the immune system during vaccination. In this study, we investigated whether crude polysaccharides derived from carrot pomace (CPP) could stimulate innate immune cell function and promote influenza vaccine immunogenicity. In bone marrow-derived dendritic cells (BMDCs), CPP increased the fraction of CD11c+MHCII+ cells and the expression of co-stimulatory molecules CD40 and CD80, indicative of enhanced maturation and activation. Functionally, CPP-treated BMDCs promoted inflammatory cytokine production in splenic lymphocytes. In a mouse model of immunosuppression induced by cyclophosphamide, animals given CPP before and after an influenza vaccine challenge showed increased frequencies of dendritic cells and natural killer cells in the spleen, in addition to the recovery of vaccine-specific antibody titers. Moreover, innate myeloid cells in CPP-fed mice showed evidence of phenotypic modification via markedly enhanced interleukin(IL)-12 and interferon(IFN)-γ production in response to lipopolysaccharide(LPS) stimulation ex vivo. Our findings suggest that the administration of carrot pomace polysaccharides can significantly enhance the efficacy of influenza vaccination.

scholarly journals Leishmania Priming of Human Dendritic Cells for CD40 Ligand-Induced Interleukin-12p70 Secretion Is Strain and Species Dependent

2002 ◽  
Vol 70 (8) ◽  
pp. 3994-4001 ◽  
Author(s):  
Mary Ann McDowell ◽  
Mary Marovich ◽  
Rosalia Lira ◽  
Michael Braun ◽  
David Sacks
Keyword(s):  
Dendritic Cells ◽  
Systemic Disease ◽  
Cd40 Ligand ◽  
Surface Expression ◽  
Interleukin 12 ◽  
Pcr Analysis ◽  
Cutaneous Lesions ◽  
Major Question ◽  
Reverse Transcription Pcr ◽  
Human Dendritic Cells

ABSTRACT A major question in the study of leishmaniasis is what dictates clinical disease expression produced by different Leishmania species, i.e., cutaneous versus systemic and healing versus nonhealing. Animal models using a Leishmania species associated with self-limiting cutaneous disease (L. major) have revealed that protective immunity requires CD40/CD40 ligand (CD40L)-dependent, interleukin-12 (IL-12)-driven Th1 responses. We recently showed that L. major can prime human dendritic cells (DCs) for CD40L-triggered IL-12p70 secretion and that these cells can drive a Th1 response in autologous T cells from sensitized individuals. Here we show that in contrast to L. major, Leishmania species responsible for visceral disease (L. donovani), as well as species associated with persistent, cutaneous lesions and occasional systemic disease (L. tropica), did not induce CD40L-dependent IL-12p70 production, despite comparable levels of uptake by DCs. Up-regulated surface expression of CD40 did not correlate with IL-12p70 production, and appreciable CD40L-induced IL-12p40 secretion was observed in uninfected as well as infected DCs, regardless of species. Reverse transcription-PCR analysis confirmed that the production of heterodimeric IL-12 was limited by expression of IL-12p35 mRNA, which was dependent on both a microbial priming signal and CD40 engagement for its high-level induction. The intrinsic differences in the ability of Leishmania species to prime DCs for CD40L-dependent IL-12p70 secretion may account, at least in part, for the evolution of healing and nonhealing forms of leishmanial disease.

scholarly journals Maturation of Human Dendritic Cells by Cell Wall Skeleton of Mycobacterium bovis Bacillus Calmette-Guérin: Involvement of Toll-Like Receptors

2000 ◽  
Vol 68 (12) ◽  
pp. 6883-6890 ◽  
Author(s):  
Shoutaro Tsuji ◽  
Misako Matsumoto ◽  
Osamu Takeuchi ◽  
Shizuo Akira ◽  
Ichiro Azuma ◽  
...  
Keyword(s):  
Cell Wall ◽  
Dendritic Cells ◽  
Mycobacterium Bovis ◽  
Surface Expression ◽  
Necrosis Factor Alpha ◽  
Mycolic Acids ◽  
Tnf Α ◽  
Toll Like Receptor 2 ◽  
Factor Alpha ◽  
Human Dendritic Cells

ABSTRACT The constituents of mycobacteria are an effective immune adjuvant, as observed with complete Freund's adjuvant. In this study, we demonstrated that the cell wall skeleton of Mycobacterium bovis bacillus Calmette-Guérin (BCG-CWS), a purified noninfectious material consisting of peptidoglycan, arabinogalactan, and mycolic acids, induces maturation of human dendritic cells (DC). Surface expression of CD40, CD80, CD83, and CD86 was increased by BCG-CWS on human immature DC, and the effect was similar to those of interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), heat-killed BCG, and viable BCG. BCG-CWS induced the secretion of TNF-α, IL-6, and IL-12 p40. CD83 expression was increased by a soluble factor secreted from BCG-CWS-treated DC and was completely inhibited by monoclonal antibodies against TNF-α. BCG-CWS-treated DC stimulated extensive allogeneic mixed lymphocyte reactions. The level of TNF-α secreted through BCG-CWS was partially suppressed in murine macrophages with no Toll-like receptor 2 (TLR 2) or TLR4 and was completely lost in TLR2 and TLR4 double-deficient macrophages. These results suggest that the BCG-CWS induces TNF-α secretion from DC via TLR2 and TLR4 and that the secreted TNF-α induces the maturation of DC per se.

scholarly journals Infection of Human Dendritic Cells with a Mycobacterium tuberculosis sigE Mutant Stimulates Production of High Levels of Interleukin-10 but Low Levels of CXCL10: Impact on the T-Cell Response

2006 ◽  
Vol 74 (6) ◽  
pp. 3296-3304 ◽  
Author(s):  
Elena Giacomini ◽  
Ambar Sotolongo ◽  
Elisabetta Iona ◽  
Martina Severa ◽  
Maria Elena Remoli ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Mycobacterium Tuberculosis ◽  
Human Monocyte ◽  
Interleukin 10 ◽  
T Cell Response ◽  
Interleukin 12 ◽  
Necrosis Factor Alpha ◽  
Effector Cells ◽  
Human Dendritic Cells

ABSTRACT The Mycobacterium tuberculosis genome encodes 13 sigma factors. We have previously shown that mutations in some of these transcriptional activators render M. tuberculosis sensitive to various environmental stresses and can attenuate the virulence phenotype. In this work, we focused on extracytoplasmic factor σE and studied the effects induced by the deletion of its structural gene (sigE) in the infection of human monocyte-derived dendritic cells (MDDC). We found that the wild-type M. tuberculosis strain (H37Rv), the sigE mutant (ST28), and the complemented strain (ST29) were able to infect dendritic cells (DC) to similar extents, although at 4 days postinfection a reduced ability to grow inside MDDC was observed for the sigE mutant ST28. After mycobacterium capture, the majority of MDDC underwent full maturation and expressed both inflammatory cytokines, such as tumor necrosis factor alpha, and the regulatory cytokines interleukin-12 (IL-12), IL-18, and beta interferon (IFN-β). Conversely, a higher level of production of IL-10 was observed in ST28-infected MDDC compared to H37Rv- or ST29-infected cell results. However, in spite of the presence of IL-10, supernatants from ST28-infected DC induced IFN-γ production by T cells similarly to those from H37Rv-infected DC culture. On the other hand, IL-10 impaired CXCL10 production in sigE mutant-infected DC and, indeed, its neutralization restored CXCL10 secretion. In line with these results, supernatants from ST28-infected cells showed a decreased capability to recruit CXCR3+ CD4+ T cells compared to those obtained from H37Rv-infected DC culture. Thus, our findings suggest that the sigE mutant-induced secretion of IL-10 inhibits CXCL10 expression and, in turn, the recruitment of activated-effector cells involved in the formation of granulomas.

Natural-killer cells and dendritic cells: “l'union fait la force”

Blood ◽  
2005 ◽  
Vol 106 (7) ◽  
pp. 2252-2258 ◽  
Author(s):  
Thierry Walzer ◽  
Marc Dalod ◽  
Scott H. Robbins ◽  
Laurence Zitvogel ◽  
Eric Vivier
Keyword(s):  
Dendritic Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Cell Activation ◽  
Nk Cell ◽  
Interleukin 12 ◽  
Cell Contact ◽  
Ifn Γ

AbstractSeveral recent publications have focused on the newly described interactions between natural-killer (NK) cells and dendritic cells (DCs). Activated NK cells induce DC maturation either directly or in synergy with suboptimal levels of microbial signals. Immature DCs appear susceptible to autologous NK-cell-mediated cytolysis while mature DCs are protected. NK-cell-induced DC activation is dependent on both tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ) secretion and a cell-cell contact involving NKp30. In vitro, interleukin-12 (IL-12)/IL-18, IL-15, and IFN-α/β production by activated DCs enhance, in turn, NK-cell IFN-γ production, proliferation, and cytotoxic potential, respectively. In vivo, NK-cell/DC interactions may occur in lymphoid organs as well as in nonlymphoid tissues, and their consequences are multiple. By inducing DC activation, NK-cell activation induced by tumor cells can indirectly promote antitumoral T-cell responses. Reciprocally, DCs activated through Toll-like receptors (TLRs) induce potent NK-cell activation in antiviral responses. Thus, DCs and NK cells are equipped with complementary sets of receptors that allow the recognition of various pathogenic agents, emphasizing the role of NK-cell/DC crosstalk in the coordination of innate and adaptive immune responses.

scholarly journals The Antituberculosis Drug Pyrazinamide Affects the Course of Cutaneous Leishmaniasis In Vivo and Increases Activation of Macrophages and Dendritic Cells

2009 ◽  
Vol 53 (12) ◽  
pp. 5114-5121 ◽  
Author(s):  
Susana Mendez ◽  
Ryan Traslavina ◽  
Meleana Hinchman ◽  
Lu Huang ◽  
Patricia Green ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Leishmania Major ◽  
Parasite Burden ◽  
Interleukin 12 ◽  
Toll Like Receptor ◽  
Proinflammatory Response ◽  
Necrosis Factor Alpha ◽  
Development Of Resistance ◽  
Tuberculosis Chemotherapy

ABSTRACT Antileishmanial therapy is suboptimal due to toxicity, high cost, and development of resistance to available drugs. Pyrazinamide (PZA) is a constituent of short-course tuberculosis chemotherapy. We investigated the effect of PZA on Leishmania major promastigote and amastigote survival. Promastigotes were more sensitive to the drug than amastigotes, with concentrations at which 50% of parasites were inhibited (MIC50) of 16.1 and 8.2 μM, respectively (48 h posttreatment). Moreover, 90% of amastigotes were eliminated at 120 h posttreatment, indicating that longer treatments will result in parasite elimination. Most strikingly, PZA treatment of infected C57BL/6 mice resulted in protection against disease and in a 100-fold reduction in the parasite burden. PZA treatment of J774 cells and bone marrow-derived dendritic cells and macrophages increased interleukin 12, tumor necrosis factor alpha, and activation marker expression, as well as nitric oxide production, suggesting that PZA enhances effective immune responses against the parasite. PZA treatment also activates dendritic cells deficient in Toll-like receptor 2 and 4 expression to initiate a proinflammatory response, confirming that the immunostimulatory effect of PZA is directly caused by the drug and is independent of Toll-like receptor stimulation. These results not only are strongly indicative of the promise of PZA as an alternative antileishmanial chemotherapy but also suggest that PZA causes collateral immunostimulation, a phenomenon that has never been reported for this drug.

scholarly journals The Presence of Capsule in Cryptococcus neoformans Influences the Gene Expression Profile in Dendritic Cells during Interaction with the Fungus

2008 ◽  
Vol 76 (4) ◽  
pp. 1581-1589 ◽  
Author(s):  
P. Lupo ◽  
Y. C. Chang ◽  
B. L. Kelsall ◽  
J. M. Farber ◽  
D. Pietrella ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dendritic Cells ◽  
Cryptococcus Neoformans ◽  
Antigen Processing ◽  
Virulent Strain ◽  
Interleukin 12 ◽  
Avirulent Strain ◽  
Necrosis Factor Alpha ◽  
True Nature ◽  
Polysaccharide Capsule

ABSTRACT The aim of this investigation was to study the effect of polysaccharide capsule on the gene expression in dendritic cells (DC) during their interaction with Cryptococcus neoformans. To this end, we used an encapsulated virulent strain of C. neoformans and a cap59 gene-disrupted acapsular avirulent strain derived from the same genetic background. DC were exposed to encapsulated and acapsular C. neoformans strains for 4 h and 18 h, and their transcriptional profiles were analyzed using the Affymetrix mouse gene chip U74Av2. A large number of DC genes were up-regulated after treatment with the acapsular strain. In particular, we observed the up-regulation of the genes involved in DC maturation, such as cell surface receptors, cytokines, and chemokines (interleukin-12 [IL-12], IL-2, IL-1α, IL-1β, IL-6, IL-10, tumor necrosis factor alpha, CCR7, CCL17, CCL22, CCL3, CCL4, CCL7, and CXCL10), membrane proteins, and the genes involved in antigen processing and presentation as well as cell cycle or apoptosis. The chemokine gene expression data were confirmed by real-time reverse transcription-PCR, while the expression of cytokine genes was correlated with their secretion. A completely different pattern of gene expression was observed for DC treated with an encapsulated strain of C. neoformans. In particular, no significant induction was observed in the expression of the genes mentioned above. Moreover, a number of genes, such as those coding for chemokines, were down-regulated. These results suggest that the polysaccharide capsule shrouding the cell wall of C. neoformans plays a fundamental role in inducing DC response, highlighting the molecular basis of the true nature of immune silencing exerted by capsular material.

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