EFFECT OF MEASLES VACCINE ON MATURATION OF HUMAN DENDRITIC CELLS IN VITRO

The most important means of measles control is live measles vaccine, the high epidemiological effectiveness of which is confirmed by half a century of its use. There is a question of the need to further improve the effectiveness of vaccine prophylaxis, in particular, by increasing the immunogenicity of the used vaccine given the increase in the morbidity of measles in recent years. Investigation of effect features of existing vaccine variants is necessary to identify possible ways to increase their immunogenicity. We investigated the effect of measles culture live vaccine on the maturation of human dendritic cells – the most specialized antigen-presenting cells involved in the induction of an immune response. In vitro incubation of monocytic derived immature dendritic cells with the vaccine initiates the process of their partial maturation, which is manifested in an increase in the number of cells carrying molecules CD86, CD83 and ICOSL (CD275).At the same time they have a reduced expression level of the HLA-DR molecule and chemokine receptors CCR7 and CXCR5 involved in the migration of dendritic cells to peripheral lymphoid organs. In our opinion, the relative weak side of measles vaccine effect on dendritic cell maturation is a factor limiting the immunogenicity of the vaccine, which must be taken into account when developing new measles vaccines.

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Fimbriated Porphyromonas gingivalis Is More Efficient than Fimbria-Deficient P. gingivalis in Entering Human Dendritic Cells In Vitro and Induces an Inflammatory Th1 Effector Response

Infection and Immunity ◽

10.1128/iai.72.3.1725-1732.2004 ◽

2004 ◽

Vol 72 (3) ◽

pp. 1725-1732 ◽

Cited By ~ 67

Author(s):

Ravi Jotwani ◽

Christopher W. Cutler

Keyword(s):

Dendritic Cells ◽

Porphyromonas Gingivalis ◽

Cell Metabolism ◽

Necrosis Factor Alpha ◽

Immature Dendritic Cells ◽

Factor Alpha ◽

Ifn Γ ◽

Gingival Mucosa ◽

Human Dendritic Cells

ABSTRACT Porphyromonas gingivalis is a fimbriated mucosal pathogen implicated in chronic periodontitis (CP). The fimbriae are required for invasion of the gingival mucosa and for induction of CP in animal models of periodontitis. CP is associated with infection of immature dendritic cells (DCs) by P. gingivalis in situ and with increased numbers of dermal DCs (DDCs) and mature DCs in the lamina propria. The role of fimbriae in gaining entry into human DCs and how this modulates the inflammatory and effector immune responses, however, have not been explored. To address this, we generated monocyte-derived DCs (MDDCs) in vitro which phenotypically and functionally resemble DDCs. We show here that virulent fimbriated P. gingivalis 381, in contrast to its fimbria-deficient mutant, P. gingivalis DPG3, efficiently gains entry to MDDCs in a manner dependent on active cell metabolism and cytoskeletal rearrangement. In addition, uptake of 381, unlike DPG3, induces DCs to undergo maturation, upregulate costimulatory molecules, and secrete inflammation cytokines interleukin-1β (IL-1β), IL-6, tumor necrosis factor alpha, IL-10, and IL-12. Moreover, MDDCs pulsed with 381 also stimulated a higher autologous mixed lymphocyte reaction and induced a Th1-type response, with gamma interferon (IFN-γ) being the main cytokine. Monocytes used as controls demonstrated fimbria-dependent uptake of 381 as well but produced low levels of inflammatory cytokines compared to MDDCs. When MDDCs were pulsed with recombinant fimbrillin of P. gingivalis (10 μg/ml), maturation of MDDCs was also induced; moreover, matured MDDCs induced proliferation of autologous CD4+ T cells and release of IFN-γ. Thus, these results establish the significance of P. gingivalis fimbriae in the uptake of P. gingivalis by MDDCs and in induction of immunostimulatory Th1 responses.

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Chronic and Acute Alcohol Exposure Prevents Monocyte-Derived Dendritic Cells from Differentiating and Maturing

International Journal of Immunopathology and Pharmacology ◽

10.1177/039463200802100417 ◽

2008 ◽

Vol 21 (4) ◽

pp. 929-939 ◽

Cited By ~ 10

Author(s):

B. Buttari ◽

E. Profumo ◽

R. Mancinelli ◽

U. Cesta Incani ◽

M.E. Tosti ◽

...

Keyword(s):

Dendritic Cells ◽

Immune Responses ◽

Healthy Subjects ◽

Alcohol Exposure ◽

Hla Dr ◽

Maturation In Vitro ◽

Tnf Α ◽

Human Dendritic Cells ◽

And Control

Increasing evidence suggests that alcohol abuse may be linked to adverse immunomodulatory effects on immune responses. Our study was undertaken to clarify the immunological consequences of chronic and acute alcohol exposure on differentiation and maturation of human dendritic cells (DCs). Using immunochemical and cytofluorimetric analysis we determined the phenotype and functions of monocyte-derived DCs from alcoholics and healthy subjects and analyzed their ability to respond to lipopolysaccharide (LPS) in the presence or absence of ethanol (EtOH) exposure. Our results showed that alcoholics' monocytes differentiated to immature DCs with altered phenotype and functions (alc-iDCs). Alc-iDCs showed fewer CD1a+ cells, weaker CD86 expression and higher HLA-DR expression associated with lower endocytosis and allostimulatory functions than iDCs from healthy subjects (control-iDCs). Despite these impairments, alc-iDCs produced TNF-α and IL-6 in large amounts. LPS stimulation failed to induce full phenotypical and functional alc-iDC maturation. In vitro acute EtOH exposure also prevented alc-iDCs and control-iDCs from maturing in response to LPS. T-cell priming experiments showed that EtOH treatment prevented LPS-stimulated control-iDCs from priming and polarizing naïve allogeneic T cells into Th1 cells, thus favouring a predominant Th2 environment. Collectively, our results provide evidence that chronic and acute alcohol exposure prevents DCs from differentiating and maturing in response to a microbial stimulus.

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Methods of Studying Human Dendritic Cells Applicable to Assessing Vaccine Efficacy

ЗДОРОВЬЕ НАСЕЛЕНИЯ И СРЕДА ОБИТАНИЯ - ЗНиСО / PUBLIC HEALTH AND LIFE ENVIRONMENT ◽

10.35627/2219-5238/2021-337-4-87-94 ◽

2021 ◽

pp. 87-94

Author(s):

VYu Talayev ◽

MV Svetlova ◽

IY Zaichenko ◽

ON Babaykina ◽

EV Voronina

Keyword(s):

Immune Response ◽

Dendritic Cells ◽

Immune System ◽

Quantitative Methods ◽

Effective Means ◽

Dendritic Cell Maturation ◽

Primary Immune Response ◽

Human Immune System ◽

Human Dendritic Cells

Introduction: Vaccines are one of the most effective means of preventing infectious diseases. Their effectiveness and safety are guaranteed by studies of vaccine properties, during their development and during the mandatory preclinical and clinical trials of each new vaccine. Additional information on the mechanisms of vaccine action on human immune system cells can be obtained using in vitro immune response models. The objective of the study was to determine applicability of certain methods of studying human dendritic cells in vitro to assessing the effect of vaccines. Dendritic cells are the most active antigen presenting cells, which play a key role in triggering a primary immune response to an infection or vaccine. Materials and methods: We studied the effect of vaccines on the maturation of dendritic cells, their phagocytic activity and the ability to stimulate T-lymphocytes in vitro. Results: To test the methods, we used vaccines with a known pattern of action on the immune system. All the vaccines induced the expression of dendritic cell maturation markers. At the same time, different vaccines induced a different set of markers and the degree of expression of these molecules. Quantitative methods for assessing phagocytosis and stimulating activity of dendritic cells are described. Conclusion: Methods for evaluation of phagocytosis, phenotypic maturation and functional properties of dendritic cells have been shown to be useful for evaluation of vaccine action. In our opinion, these methods, as a complement to traditional methods for evaluating the immune response, can be used to investigate the action of prototype vaccines at the stage of their development and preclinical trials.

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Wegener autoantigen induces maturation of dendritic cells and licenses them for Th1 priming via the protease-activated receptor-2 pathway

Blood ◽

10.1182/blood-2005-05-1875 ◽

2006 ◽

Vol 107 (11) ◽

pp. 4440-4448 ◽

Cited By ~ 74

Author(s):

Elena Csernok ◽

MaiXing Ai ◽

Wolfgang L. Gross ◽

Daniel Wicklein ◽

Arnd Petersen ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Cd4 T Cells ◽

T Helper 1 ◽

Wegener Granulomatosis ◽

Immature Dendritic Cells ◽

Hla Dr ◽

Ifn Γ ◽

Protease Activated Receptor 2

Abstract Autoantibodies to proteinase 3 (PR3) are involved in the pathogenesis of autoimmune-mediated vasculitis in Wegener granulomatosis (WG). To address the question how the autoantigen PR3 becomes a target of adaptive immunity, we investigated the effect of PR3 on immature dendritic cells (iDCs) in patients with WG, healthy blood donors, and patients with Crohn disease (CD), another granulomatous disease. PR3 induces phenotypic and functional maturation of a fraction of blood monocyte-derived iDCs. PR3-treated DCs express high levels of CD83, a DC-restricted marker of maturation, CD80 and CD86, and HLA-DR. Furthermore, the DCs become fully competent antigen-presenting cells and can induce stimulation of PR3-specific CD4+ T cells, which produce IFN-γ. PR3-maturated DCs derived from WG patients induce a higher IFN-γ response of PR3-specific CD4+ T cells compared with patients with CD and healthy controls. The maturation of DCs mediated through PR3 was inhibited by a serine protease inhibitor, by antibodies directed against the protease-activated receptor-2 (PAR-2), and by inhibition of phospholipase C, suggesting that the interactions of PR3 with PAR-2 are involved in the induction of DC maturation. Wegener autoantigen interacts with a “gateway” receptor (PAR-2) on iDCs in vitro triggering their maturation and licenses them for a T helper 1 (Th1)–type response potentially favoring granuloma formation in WG.

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Faculty Opinions recommendation of The interaction of human dendritic cells with yeast and germ-tube forms of Candida albicans leads to efficient fungal processing, dendritic cell maturation, and acquisition of a Th1 response-promoting function.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1016239.199628 ◽

2003 ◽

Author(s):

Emanuela Handman

Keyword(s):

Dendritic Cells ◽

Candida Albicans ◽

Dendritic Cell ◽

Germ Tube ◽

Dendritic Cell Maturation ◽

Cell Maturation ◽

Th1 Response ◽

Human Dendritic Cells

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Faculty Opinions recommendation of Ascaris suum infection downregulates inflammatory pathways in the pig intestine in vivo and in human dendritic cells in vitro.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732114816.793551813 ◽

2018 ◽

Author(s):

Thomas Nutman

Keyword(s):

Dendritic Cells ◽

Ascaris Suum ◽

Inflammatory Pathways ◽

Human Dendritic Cells

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Effects of Staphylococcus aureus Bacteriophage K on Expression of Cytokines and Activation Markers by Human Dendritic Cells In Vitro

Viruses ◽

10.3390/v10110617 ◽

2018 ◽

Vol 10 (11) ◽

pp. 617 ◽

Cited By ~ 5

Author(s):

Helen Freyberger ◽

Yunxiu He ◽

Amanda Roth ◽

Mikeljon Nikolich ◽

Andrey Filippov

Keyword(s):

Staphylococcus Aureus ◽

Dendritic Cells ◽

Inflammatory Response ◽

Adaptive Immune Response ◽

Human Monocyte ◽

Activation Markers ◽

Mhc I ◽

Adaptive Immune ◽

Human Dendritic Cells

A potential concern with bacteriophage (phage) therapeutics is a host-versus-phage response in which the immune system may neutralize or destroy phage particles and thus impair therapeutic efficacy, or a strong inflammatory response to repeated phage exposure might endanger the patient. Current literature is discrepant with regard to the nature and magnitude of innate and adaptive immune response to phages. The purpose of this work was to study the potential effects of Staphylococcus aureus phage K on the activation of human monocyte-derived dendritic cells. Since phage K acquired from ATCC was isolated around 90 years ago, we first tested its activity against a panel of 36 diverse S. aureus clinical isolates from military patients and found that it was lytic against 30/36 (83%) of strains. Human monocyte-derived dendritic cells were used to test for an in vitro phage-specific inflammatory response. Repeated experiments demonstrated that phage K had little impact on the expression of pro- and anti-inflammatory cytokines, or on MHC-I/II and CD80/CD86 protein expression. Given that dendritic cells are potent antigen-presenting cells and messengers between the innate and the adaptive immune systems, our results suggest that phage K does not independently affect cellular immunity or has a very limited impact on it.

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Regulatory perspective on in vitro potency assays for human dendritic cells used in anti-tumor immunotherapy

Cytotherapy ◽

10.1016/j.jcyt.2018.07.006 ◽

2018 ◽

Vol 20 (11) ◽

pp. 1289-1308 ◽

Cited By ~ 2

Author(s):

CHARLOTTE DE Wolf ◽

MARJA VAN DE BOVENKAMP ◽

MARCEL HOEFNAGEL

Keyword(s):

Dendritic Cells ◽

Tumor Immunotherapy ◽

Regulatory Perspective ◽

Human Dendritic Cells

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Inhibition of O-GlcNAc Transferase Alters the Differentiation and Maturation Process of Human Monocyte Derived Dendritic Cells

Cells ◽

10.3390/cells10123312 ◽

2021 ◽

Vol 10 (12) ◽

pp. 3312

Author(s):

Matjaž Weiss ◽

Marko Anderluh ◽

Martina Gobec

Keyword(s):

Dendritic Cells ◽

Posttranslational Modification ◽

Human Monocyte ◽

T Cell Differentiation ◽

Maturation Process ◽

Hla Dr ◽

Glcnac Transferase ◽

And Function

The O-GlcNAcylation is a posttranslational modification of proteins regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase. These enzymes regulate the development, proliferation and function of cells, including the immune cells. Herein, we focused on the role of O-GlcNAcylation in human monocyte derived dendritic cells (moDCs). Our study suggests that inhibition of OGT modulates AKT and MEK/ERK pathways in moDCs. Changes were also observed in the expression levels of relevant surface markers, where reduced expression of CD80 and DC-SIGN, and increased expression of CD14, CD86 and HLA-DR occurred. We also noticed decreased IL-10 and increased IL-6 production, along with diminished endocytotic capacity of the cells, indicating that inhibition of O-GlcNAcylation hampers the transition of monocytes into immature DCs. Furthermore, the inhibition of OGT altered the maturation process of immature moDCs, since a CD14medDC-SIGNlowHLA-DRmedCD80lowCD86high profile was noticed when OGT inhibitor, OSMI-1, was present. To evaluate DCs ability to influence T cell differentiation and polarization, we co-cultured these cells. Surprisingly, the observed phenotypic changes of mature moDCs generated in the presence of OSMI-1 led to an increased proliferation of allogeneic T cells, while their polarization was not affected. Taken together, we confirm that shifting the O-GlcNAcylation status due to OGT inhibition alters the differentiation and function of moDCs in in vitro conditions.

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