HDAC inhibition by LBH589 affects the phenotype and function of human myeloid dendritic cells

In many subjects who are genetically susceptible to asthma, exposure to environmental stimuli may exacerbate their condition. However, it is unknown how the expression and function of a family of pattern-recognition receptors called toll-like receptors (TLR) are affected by exposure to particulate pollution. TLRs serve a critical function in alerting the immune system of tissue damage or infection—the so-called “danger signals”. We are interested in the role that TLRs play in directing appropriate responses by innate immunity, particularly dendritic cells (DC), after exposing them to particulate pollution. Dendritic cells serve a pivotal role in directing host immunity. Thus, we hypothesized that alterations in TLR expression could be further explored as potential biomarkers of effect related to DC exposure to particulate pollution. We show some preliminary data that indicates that inhaled particulate pollution acts directly on DC by down-regulating TLR expression and altering the activation state of DC. While further studies are warranted, we suggest that alterations in TLR2 and TLR4 expression should be explored as potential biomarkers of DC exposure to environmental particulate pollution.

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Phenotype and function of myeloid dendritic cells derived from African green monkey blood monocytes

Journal of Immunological Methods ◽

10.1016/j.jim.2005.10.005 ◽

2006 ◽

Vol 308 (1-2) ◽

pp. 138-155 ◽

Cited By ~ 18

Author(s):

Lorenzo Mortara ◽

Mickaël J.-Y. Ploquin ◽

Abdourahmane Faye ◽

Daniel Scott-Algara ◽

Bruno Vaslin ◽

...

Keyword(s):

Dendritic Cells ◽

African Green Monkey ◽

Blood Monocytes ◽

Myeloid Dendritic Cells ◽

Green Monkey ◽

And Function

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Branched chain amino acids enhance the maturation and function of myeloid dendritic cells ex vivo in patients with advanced cirrhosis

Hepatology ◽

10.1002/hep.23248 ◽

2009 ◽

Vol 50 (6) ◽

pp. 1936-1945 ◽

Cited By ~ 41

Author(s):

Eiji Kakazu ◽

Yoshiyuki Ueno ◽

Yasuteru Kondo ◽

Koji Fukushima ◽

Masaaki Shiina ◽

...

Keyword(s):

Amino Acids ◽

Dendritic Cells ◽

Ex Vivo ◽

Branched Chain Amino Acids ◽

Myeloid Dendritic Cells ◽

Advanced Cirrhosis ◽

Branched Chain ◽

And Function

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Dendritic cell responses to Plasmodium falciparum in a malaria-endemic setting

10.21203/rs.3.rs-72313/v2 ◽

2020 ◽

Author(s):

Triniti C. Turner ◽

Charles Arama ◽

Aissata Ongoiba ◽

Safiatou Doumbo ◽

Didier Doumtabé ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Dendritic Cells ◽

Dendritic Cell ◽

Peripheral Blood ◽

Dendritic Cell Subset ◽

Myeloid Dendritic Cells ◽

Hla Dr ◽

Malaria Exposure ◽

History Of ◽

And Function

Abstract Background: Plasmodium falciparum causes the majority of malaria cases world-wide, mostly affecting children in sub-Saharan Africa. Non-sterile clinical immunity that protects from symptoms develops slowly and is relatively short-lived. Moreover, current malaria vaccine candidates fail to induce durable high-level protection in endemic settings, possibly due to the immunomodulatory effects of the malaria parasite itself. Because dendritic cells play a crucial role in initiating immune responses, here we sought to better understand the impact of cumulative malaria exposure as well as concurrent P. falciparum infection on dendritic cell phenotype and function.Methods: In this cross-sectional study we assessed the phenotype and function of dendritic cells freshly isolated from peripheral blood samples of Malian adults with a lifelong history of malaria exposure who were either uninfected (n=27) or asymptomatically infected with P. falciparum (n=8). Additionally, we measured plasma cytokine and chemokine levels in these adults and in Malian children (n=19) with acute symptomatic malaria.Results: With the exception of lower plasmacytoid dendritic cell frequencies in asymptomatically infected Malian adults, peripheral blood dendritic cell subset frequencies and HLA-DR surface expression did not differ by infection status. Peripheral blood myeloid dendritic cells of uninfected Malian adults responded to in vitro stimulation with P. falciparum blood-stage parasites by up-regulating the costimulatory molecules HLA-DR, CD80, CD86 and CD40 and secreting IL-10, CXCL9 and CXCL10. In contrast, myeloid dendritic cells of asymptomatically infected Malian adults exhibited no significant responses above the uninfected red blood cell control. IL-10 and CXCL9 plasma levels were elevated in both asymptomatic adults and children with acute malaria.Conclusions: Our findings indicate that myeloid dendritic cells of uninfected adults with a lifelong history of malaria exposure are able to up-regulate co-stimulatory molecules and produce cytokines. Whether mDCs of malaria-exposed individuals are efficient antigen-presenting cells capable of mounting an appropriate immune response remains to be determined. The data also highlights IL-10 and CXCL9 as important factors in both asymptomatic and acute malaria and add to our understanding of asymptomatic P. falciparum infections in malaria-endemic areas.

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Dendritic cell responses to Plasmodium falciparum in a malaria-endemic setting

10.21203/rs.3.rs-72313/v1 ◽

2020 ◽

Author(s):

Triniti C. Turner ◽

Charles Arama ◽

Aissata Ongoiba ◽

Safiatou Doumbo ◽

Didier Doumtabé ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Dendritic Cells ◽

Dendritic Cell ◽

Peripheral Blood ◽

Dendritic Cell Subset ◽

Myeloid Dendritic Cells ◽

Hla Dr ◽

Malaria Exposure ◽

History Of ◽

And Function

Abstract Background: Plasmodium falciparum causes the majority of malaria cases world-wide, mostly affecting children in sub-Saharan Africa. Non-sterile clinical immunity that protects from symptoms develops slowly and is relatively short-lived. Moreover, current malaria vaccine candidates fail to induce durable high-level protection in endemic settings, possibly due to the immunomodulatory effects of the malaria parasite itself. Because dendritic cells play a crucial role in initiating immune responses, here we sought to better understand the impact of cumulative malaria exposure as well as concurrent P. falciparum infection on dendritic cell phenotype and function.Methods: In this cross-sectional study we assessed the phenotype and function of dendritic cells freshly isolated from peripheral blood samples of Malian adults with a lifelong history of malaria exposure who were either uninfected (n=27) or asymptomatically infected with P. falciparum (n=8). Additionally, we measured plasma cytokine and chemokine levels in these adults and in Malian children (n=19) with acute symptomatic malaria.Results: With the exception of lower plasmacytoid dendritic cell frequencies in asymptomatically infected Malian adults, peripheral blood dendritic cell subset frequencies and HLA-DR surface expression did not differ by infection status. Peripheral blood myeloid dendritic cells of uninfected Malian adults responded to in vitro stimulation with P. falciparum blood-stage parasites by up-regulating the costimulatory molecules HLA-DR, CD80, CD86 and CD40 and secreting IL-10, CXCL9 and CXCL10. In contrast, myeloid dendritic cells of asymptomatically infected Malian adults exhibited no significant responses above the uninfected red blood cell control. IL-10 and CXCL9 plasma levels were elevated in both asymptomatic adults and children with acute malaria.Conclusions: Our findings indicate that myeloid dendritic cells of uninfected adults with a lifelong history of malaria exposure are able to up-regulate co-stimulatory molecules and produce cytokines in a manner that is comparable to mDCs of malaria-naïve individuals. Whether mDCs of malaria-exposed individuals are efficient antigen-presenting cells capable of mounting an appropriate immune response remains to be determined. The data also highlights IL-10 and CXCL9 as important factors in both asymptomatic and acute malaria and add to our understanding of asymptomatic P. falciparum infections in malaria-endemic areas.

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Dendritic cell responses to Plasmodium falciparum in a malaria-endemic setting

10.21203/rs.3.rs-72313/v3 ◽

2020 ◽

Author(s):

Triniti C. Turner ◽

Charles Arama ◽

Aissata Ongoiba ◽

Safiatou Doumbo ◽

Didier Doumtabé ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Dendritic Cells ◽

Dendritic Cell ◽

Peripheral Blood ◽

Dendritic Cell Subset ◽

Myeloid Dendritic Cells ◽

Hla Dr ◽

Malaria Exposure ◽

History Of ◽

And Function

Abstract Background Plasmodium falciparum causes the majority of malaria cases worldwide and children in sub-Saharan Africa are the most vulnerable group affected. Non-sterile clinical immunity that protects from symptoms develops slowly and is relatively short-lived. Moreover, current malaria vaccine candidates fail to induce durable high-level protection in endemic settings, possibly due to the immunomodulatory effects of the malaria parasite itself. Because dendritic cells play a crucial role in initiating immune responses, the aim of this study was to better understand the impact of cumulative malaria exposure as well as concurrent P. falciparum infection on dendritic cell phenotype and function.Methods In this cross-sectional study, the phenotype and function of dendritic cells freshly isolated from peripheral blood samples of Malian adults with a lifelong history of malaria exposure who were either uninfected (n=27) or asymptomatically infected with P. falciparum (n=8) was assessed. Additionally, plasma cytokine and chemokine levels were measured in these adults and in Malian children (n=19) with acute symptomatic malaria.Results With the exception of lower plasmacytoid dendritic cell frequencies in asymptomatically infected Malian adults, peripheral blood dendritic cell subset frequencies and HLA-DR surface expression did not differ by infection status. Peripheral blood myeloid dendritic cells of uninfected Malian adults responded to in vitro stimulation with P. falciparum blood-stage parasites by up-regulating the costimulatory molecules HLA-DR, CD80, CD86 and CD40 and secreting IL-10, CXCL9 and CXCL10. In contrast, myeloid dendritic cells of asymptomatically infected Malian adults exhibited no significant responses above the uninfected red blood cell control. IL-10 and CXCL9 plasma levels were elevated in both asymptomatic adults and children with acute malaria.Conclusions The findings of this study indicate that myeloid dendritic cells of uninfected adults with a lifelong history of malaria exposure are able to up-regulate co-stimulatory molecules and produce cytokines. Whether mDCs of malaria-exposed individuals are efficient antigen-presenting cells capable of mounting an appropriate immune response remains to be determined. The data also highlights IL-10 and CXCL9 as important factors in both asymptomatic and acute malaria and add to the understanding of asymptomatic P. falciparum infections in malaria-endemic areas.

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Monomethyl fumarate treatment impairs maturation of human myeloid dendritic cells and their ability to activate T cells

Multiple Sclerosis Journal ◽

10.1177/1352458517740213 ◽

2017 ◽

Vol 25 (1) ◽

pp. 63-71 ◽

Cited By ~ 9

Author(s):

Maria Antonietta Mazzola ◽

Radhika Raheja ◽

Keren Regev ◽

Vanessa Beynon ◽

Felipe von Glehn ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Dimethyl Fumarate ◽

Nuclear Factor Κb ◽

Interleukin 17 ◽

Myeloid Dendritic Cells ◽

Gm Csf ◽

Monomethyl Fumarate ◽

And Function

Background: Dimethyl fumarate (DMF) and its active metabolite monomethyl fumarate (MMF) effectively lead to reduction in disease relapses and active magnetic resonance imaging (MRI) lesions. DMF and MMF are known to be effective in modulating T- and B-cell responses; however, their effect on the phenotype and function of human myeloid dendritic cells (mDCs) is not fully understood. Objective: To investigate the role of MMF on human mDCs maturation and function. Methods: mDCs from healthy controls were isolated and cultured in vitro with MMF. The effect of MMF on mDC gene expression was determined by polymerase chain reaction (PCR) array after in vitro MMF treatment. The ability of mDCs to activate T cells was assessed by in vitro co-culture system. mDCs from DMF-treated multiple sclerosis (MS) patients were analyzed by flow cytometry and PCR. Results: MMF treatment induced a less mature phenotype of mDCs with reduced expression of major histocompatibility complex class II (MHC-II), co-stimulatory molecules CD86, CD40, CD83, and expression of nuclear factor κB (NF-κB) subunits RELA and RELB. mDCs from DMF-treated MS patients also showed the same immature phenotype. T cells co-cultured with MMF-treated mDCs showed reduced proliferation with decreased production of interferon gamma (IFN-γ), interleukin-17 (IL-17), and granulocyte-macrophage colony-stimulating factor (GM-CSF) compared to untreated cells. Conclusion: We report that MMF can modulate immune response by affecting human mDC function.

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Dendritic cell responses to Plasmodium falciparum in a malaria-endemic setting

Malaria Journal ◽

10.1186/s12936-020-03533-w ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Triniti C. Turner ◽

Charles Arama ◽

Aissata Ongoiba ◽

Safiatou Doumbo ◽

Didier Doumtabé ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Dendritic Cells ◽

Dendritic Cell ◽

Peripheral Blood ◽

Dendritic Cell Subset ◽

Myeloid Dendritic Cells ◽

Hla Dr ◽

Malaria Exposure ◽

History Of ◽

And Function

Abstract Background Plasmodium falciparum causes the majority of malaria cases worldwide and children in sub-Saharan Africa are the most vulnerable group affected. Non-sterile clinical immunity that protects from symptoms develops slowly and is relatively short-lived. Moreover, current malaria vaccine candidates fail to induce durable high-level protection in endemic settings, possibly due to the immunomodulatory effects of the malaria parasite itself. Because dendritic cells play a crucial role in initiating immune responses, the aim of this study was to better understand the impact of cumulative malaria exposure as well as concurrent P. falciparum infection on dendritic cell phenotype and function. Methods In this cross-sectional study, the phenotype and function of dendritic cells freshly isolated from peripheral blood samples of Malian adults with a lifelong history of malaria exposure who were either uninfected (n = 27) or asymptomatically infected with P. falciparum (n = 8) was assessed. Additionally, plasma cytokine and chemokine levels were measured in these adults and in Malian children (n = 19) with acute symptomatic malaria. Results With the exception of lower plasmacytoid dendritic cell frequencies in asymptomatically infected Malian adults, peripheral blood dendritic cell subset frequencies and HLA-DR surface expression did not differ by infection status. Peripheral blood myeloid dendritic cells of uninfected Malian adults responded to in vitro stimulation with P. falciparum blood-stage parasites by up-regulating the costimulatory molecules HLA-DR, CD80, CD86 and CD40 and secreting IL-10, CXCL9 and CXCL10. In contrast, myeloid dendritic cells of asymptomatically infected Malian adults exhibited no significant responses above the uninfected red blood cell control. IL-10 and CXCL9 plasma levels were elevated in both asymptomatic adults and children with acute malaria. Conclusions The findings of this study indicate that myeloid dendritic cells of uninfected adults with a lifelong history of malaria exposure are able to up-regulate co-stimulatory molecules and produce cytokines. Whether mDCs of malaria-exposed individuals are efficient antigen-presenting cells capable of mounting an appropriate immune response remains to be determined. The data also highlights IL-10 and CXCL9 as important factors in both asymptomatic and acute malaria and add to the understanding of asymptomatic P. falciparum infections in malaria-endemic areas.

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8. Examining the Effects of Peptide-Gold Nanoparticle Hybrids on the Activation of Myeloid Dendritic Cells

Inquiry@Queen's Undergraduate Research Conference Proceedings ◽

10.24908/iqurcp.8790 ◽

2016 ◽

Author(s):

Annie Liu

Keyword(s):

Dendritic Cells ◽

Immune Modulation ◽

Immune Therapy ◽

Myeloid Dendritic Cells ◽

Gm Csf ◽

Enhanced Expression ◽

Microscope Imaging ◽

Macrophage Colony ◽

And Function

Dendritic cells (DCs) are professional antigen-presenting cells that play an important role in innate and adaptive immunity. They have become a major target for immune modulation based therapeutic strategies. Gold nanoparticles (GNPs) are biocompatible materials. The surface of GNPs can be easily modified with peptides via thiol-gold linkage to alter their surface chemistry and to modulate their cellular uptake. The purpose of this present study was to investigate the ability of peptide-GNP hybrids to modulate the DC immune response in vitro. To assess the activation effects of peptide-GNP hybrids, DCs were differentiated from bone marrow (BM) cells of black B57BL/6 mice by culture with granulocyte macrophage colony stimulating factor (GM-CSF). At day 9 of culture, BM-derived DCs (BMDCs) were exposed to GNP hybrids with a diameter of approximately 10 nm. The purity of the resulting DCs was determined by the CD11c positive cell population measured by Flow Cytometry. We found that the peptide-GNP hybrids were internalized by immature BMDC via bright field microscope imaging. Furthermore, the addition of GNPs to immature BMDCs was found to influence both phenotype and function of immature BMDCs. Stimulation by peptide-GNP hybrids on the immature BMDCs led to an enhanced expression of co-stimulatory molecules on the cell surface, including CD40, CD80 and CD86, and a secretion of cytokines in the culture medium. This observation suggests that peptide-GNP stimulation can lead to the activation of BMDCs, and implies a potential application for strengthening vaccine delivery devices or cancer immune therapy.

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