Vibrio parahaemolyticus Flagellin Stimulates the Maturation of Human Monocyte-Derived Dendritic Cells and Elicits Th1-Type Immune Response.

Abstract Flagellin, the principal component of bacterial flagella, interacts with Toll-like receptor (TLR5) and induces the generation of a pro-inflammation response and activation of host dendritic cells (DCs) in vivo. In this study, we investigated the role of Vibrio parahaemolyticus (V. parahaemolyticus)-derived flagellin as a DC maturation-inducing molecule. V. parahemolyticus-derived flagellin (100–1,000 ng/ml) induced the maturation of human monocyte-derived dendritic cells in a concentration-dependent manner with maximal effect at 500 ng/ml of flagellin as determined by increased levels of surface markers, namely, CD1a, CD80, CD86, CD83, and HLA-DR, a response which could be compared with the phenotypic change in immature DCs (iDCs) treated with lipopolysaccharide (LPS) or cytokine cocktails (CC) with TNF-α, IL-1β, IL-6, and PGE2. Moreover, V. parahaemolyticus-derived flagellin also reduced phagocytic activity, and increased IL-12 production in a polymyxin B-insensitive manner and DC-mediated T cell proliferation, which is comparable with that of LPS- or CC-treated iDCs at several responder to stimulator ratios, suggesting the functional maturation of DCs by V. parahaemolyticus-derived flagellin. Maturation of DCs by V. parahaemolyticus-derived flagellin also elicited a significant increase in specific cytotoxic activity against target cells at several effector to target cells ratios as determined by 51Cr-release assay, and induced Th1-type immune response, such as increase in INF-γ producing cells, determined by ELISPOT assay and analysis of intracellular cytokine staining assay. Taken together, this study demonstrates the role of V. parahaemolyticus-derived flagellin in the functional maturation of DCs, and suggests that V. parahaemolyticus-derived flagellin as a useful molecule for the development of a DC-based immunotherapy against tumors.

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The Role of IL-36 in the Pathophysiological Processes of Autoimmune Diseases

Frontiers in Pharmacology ◽

10.3389/fphar.2021.727956 ◽

2021 ◽

Vol 12 ◽

Author(s):

Wen-jian Chen ◽

Xiao Yu ◽

Xin-Rong Yuan ◽

Bang-jie Chen ◽

Na Cai ◽

...

Keyword(s):

Immune Response ◽

Dendritic Cells ◽

Inflammatory Response ◽

Autoimmune Diseases ◽

Future Research ◽

Dependent Manner ◽

Receptor Complexes ◽

Multiple Organs ◽

Pro Inflammatory Cytokines

A member of the interleukin (IL)-1 superfamily was IL-36, which contained IL-36α, IL-36β, IL-36γ, and IL-36Ra. Heterotrimer complexes, consisting of heterodimeric receptor complexes and IL-36 agonist, gave signals through intracellular functional domains, so as to bind to downstream proteins and induce inflammatory response. IL-36 agonists upregulated mature-associated CD80, CD86, MHCII, and inductively produced several pro-inflammatory cytokines through the IL-36R-dependent manner in dendritic cells (DCs). Besides, DCs had the ability to initiate the differentiation of helper T (Th) cells. Up to date, the role of IL-36 in immunity, inflammation and other diseases is of great importance. Additionally, autoimmune diseases were characterized by excessive immune response, resulting in damage and dysfunction of specific or multiple organs and tissues. Most autoimmune diseases were related to inflammatory response. In this review, we will conclude the recent research advances of IL-36 in the occurrence and development of autoimmune diseases, which may provide new insight for the future research and the treatment of these diseases.

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Bacillus anthracis Capsule Activates Caspase-1 and Induces Interleukin-1β Release from Differentiated THP-1 and Human Monocyte-Derived Dendritic Cells

Infection and Immunity ◽

10.1128/iai.00956-09 ◽

2009 ◽

Vol 78 (1) ◽

pp. 387-392 ◽

Cited By ~ 12

Author(s):

Min-Hee Cho ◽

Hae-Jeong Ahn ◽

Hyun-Joon Ha ◽

Jungchan Park ◽

Jeong-Hoon Chun ◽

...

Keyword(s):

Immune Response ◽

Dendritic Cells ◽

Bacillus Anthracis ◽

Innate Immune Response ◽

Human Monocyte ◽

Innate Immune ◽

Interleukin 1Β ◽

Dependent Manner ◽

Caspase 1 ◽

Extracellular Release

ABSTRACT The poly-γ-d-glutamic acid (PGA) capsule is one of the major virulence factors of Bacillus anthracis, which causes a highly lethal infection. The antiphagocytic PGA capsule disguises the bacilli from immune surveillance and allows unimpeded growth of bacilli in the host. Recently, efforts have been made to include PGA as a component of anthrax vaccine; however, the innate immune response of PGA itself has been poorly investigated. In this study, we characterized the innate immune response elicited by PGA in the human monocytic cell line THP-1, which was differentiated into macrophages with phorbol 12-myristate 13-acetate (PMA) and human monocyte-derived dendritic cells (hMoDCs). PGA capsules were isolated from the culture supernatant of either the pXO1-cured strain of B. anthracis H9401 or B. licheniformis ATCC 9945a. PGA treatment of differentiated THP-1 cells and hMoDCs led to the specific extracellular release of interleukin-1β (IL-1β) in a dose-dependent manner. Evaluation of IL-1β processing by Western blotting revealed that cleaved IL-1β increased in THP-1 cells and hMoDCs after PGA treatment. Enhanced processing of IL-1β directly correlated with increased activation of its upstream regulator, caspase-1, also known as IL-1β-converting enzyme (ICE). The extracellular release of IL-1β in response to PGA was ICE dependent, since the administration of an ICE inhibitor prior to PGA treatment blocked induction of IL-1β. These results demonstrate that B. anthracis PGA elicits IL-1β production through activation of ICE in PMA-differentiated THP-1 cells and hMoDCs, suggesting the potential for PGA as a therapeutic target for anthrax.

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The Role of Human T-Lymphotropic Virus Type 1 (HTLV-1)-Infected Dendritic Cells in the Development of HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis

Journal of Virology ◽

10.1128/jvi.73.6.4575-4581.1999 ◽

1999 ◽

Vol 73 (6) ◽

pp. 4575-4581 ◽

Cited By ~ 61

Author(s):

Masahiko Makino ◽

Satoshi Shimokubo ◽

Shin-Ichi Wakamatsu ◽

Shuji Izumo ◽

Masanori Baba

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Virus Type ◽

Spastic Paraparesis ◽

Tropical Spastic Paraparesis ◽

Normal Donor ◽

Dependent Manner ◽

T Lymphotropic Virus

ABSTRACT The development of human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is closely associated with the activation of T cells which are HTLV-1 specific but may cross-react with neural antigens (Ags). Immature dendritic cells (DCs), differentiated from normal donor monocytes by using recombinant granulocyte-macrophage colony-stimulating factor and recombinant interleukin-4, were pulsed with HTLV-1 in vitro. The pulsed DCs contained HTLV-1 proviral DNA and expressed HTLV-1 Gag Ag on their surface 6 days after infection. The DCs matured by lipopolysaccharides stimulated autologous CD4+ T cells and CD8+ T cells in a viral dose-dependent manner. However, the proliferation level of CD4+ T cells was five- to sixfold higher than that of CD8+ T cells. In contrast to virus-infected DCs, DCs pulsed with heat-inactivated virions activated only CD4+ T cells. To clarify the role of DCs in HAM/TSP development, monocytes from patients were cultured for 4 days in the presence of the cytokines. The expression of CD86 Ag on DCs was higher and that of CD1a Ag was more down-regulated than in DCs generated from normal monocytes. DCs from two of five patients expressed HTLV-1 Gag Ag. Furthermore, both CD4+ and CD8+ T cells from the patients were greatly stimulated by contact with autologous DCs pulsed with inactivated viral Ag as well as HTLV-1-infected DCs. These results suggest that DCs are susceptible to HTLV-1 infection and that their cognate interaction with T cells may contribute to the development of HAM/TSP.

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GSK-3α Inhibition in Drug-Resistant CML Cells Promotes Susceptibility to NK Cell-Mediated Lysis in an NKG2D- and NKp30-Dependent Manner

Cancers ◽

10.3390/cancers13081802 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1802

Author(s):

Nayoung Kim ◽

Mi Yeon Kim ◽

Woo Seon Choi ◽

Eunbi Yi ◽

Hyo Jung Lee ◽

...

Keyword(s):

Nk Cells ◽

Nk Cell ◽

Negative Regulator ◽

Target Cells ◽

Dependent Manner ◽

Cell Functions ◽

Cell Based Therapy ◽

Activating Receptors ◽

Gsk 3Β

Natural killer (NK) cells are innate cytotoxic lymphocytes that provide early protection against cancer. NK cell cytotoxicity against cancer cells is triggered by multiple activating receptors that recognize specific ligands expressed on target cells. We previously demonstrated that glycogen synthase kinase (GSK)-3β, but not GSK-3α, is a negative regulator of NK cell functions via diverse activating receptors, including NKG2D and NKp30. However, the role of GSK-3 isoforms in the regulation of specific ligands on target cells is poorly understood, which remains a challenge limiting GSK-3 targeting for NK cell-based therapy. Here, we demonstrate that GSK-3α rather than GSK-3β is the primary isoform restraining the expression of NKG2D ligands, particularly ULBP2/5/6, on tumor cells, thereby regulating their susceptibility to NK cells. GSK-3α also regulated the expression of the NKp30 ligand B7-H6, but not the DNAM-1 ligands PVR or nectin-2. This regulation occurred independently of BCR-ABL1 mutation that confers tyrosine kinase inhibitor (TKI) resistance. Mechanistically, an increase in PI3K/Akt signaling in concert with c-Myc was required for ligand upregulation in response to GSK-3α inhibition. Importantly, GSK-3α inhibition improved cancer surveillance by human NK cells in vivo. Collectively, our results highlight the distinct role of GSK-3 isoforms in the regulation of NK cell reactivity against target cells and suggest that GSK-3α modulation could be used to enhance tumor cell susceptibility to NK cells in an NKG2D- and NKp30-dependent manner.

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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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Polarization of Allogeneic T-Cell Responses by Influenza Virus-Infected Dendritic Cells

Journal of Virology ◽

10.1128/jvi.74.17.7738-7744.2000 ◽

2000 ◽

Vol 74 (17) ◽

pp. 7738-7744 ◽

Cited By ~ 25

Author(s):

Sangkon Oh ◽

Maryna C. Eichelberger

Keyword(s):

Immune Response ◽

T Cells ◽

Dendritic Cells ◽

Influenza Virus ◽

T Cell ◽

Interleukin 2 ◽

Dependent Manner ◽

Ifn Γ ◽

High Doses ◽

Type Response

ABSTRACT The developing immune response in the lymph nodes of mice infected with influenza virus has both Th1- and Th2-type characteristics. Modulation of the interactions between antigen-presenting cells and T cells is one mechanism that may alter the quality of the immune response. We have previously shown that the ability of dendritic cells (DC) to stimulate the proliferation of alloreactive T cells is changed by influenza virus due to viral neuraminidase (NA) activity. Here we show that DC infected with influenza virus A/PR/8/34 (PR8) stimulate T cells to produce different types of cytokines in a dose-dependent manner. Optimal amounts of the Th1-type cytokines interleukin-2 (IL-2) and gamma interferon (IFN-γ) were produced from T cells stimulated by DC infected with low doses of PR8, while the Th2-type cytokines IL-4 and IL-10 were produced only in response to DC infected with high doses of PR8. IL-2 and IFN-γ levels corresponded with T-cell proliferation and were dependent on the activity of viral NA on the DC surface. In contrast, IL-4 secretion required the treatment of T cells with NA. Since viral particles were released only from DC that are infected with high doses of PR8, our results suggest that viral NA on newly formed virus particles desialylates T-cell surface molecules to facilitate a Th2-type response. These results suggest that the activity of NA may contribute to the mixed Th-type response observed during influenza virus infection.

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Regulatory role of tryptophan degradation pathway in HLA-G expression by human monocyte-derived dendritic cells

Molecular Immunology ◽

10.1016/j.molimm.2006.01.007 ◽

2006 ◽

Vol 43 (14) ◽

pp. 2151-2160 ◽

Cited By ~ 66

Author(s):

A LOPEZ ◽

E ALEGRE ◽

J LEMAOULT ◽

E CAROSELLA ◽

A GONZALEZ

Keyword(s):

Dendritic Cells ◽

Human Monocyte ◽

Degradation Pathway ◽

Regulatory Role ◽

Tryptophan Degradation

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CD209 (DC-SIGN) – role in the work of the innate immunity and pathogen penetration

Veterinariya, Zootekhniya i Biotekhnologiya ◽

10.36871/vet.zoo.bio.202009007 ◽

2020 ◽

Vol 1 (9) ◽

pp. 64-71

Author(s):

E. A. Klimov ◽

◽

E. K. Novitskaya ◽

S. N. Koval’chuk ◽

◽

...

Keyword(s):

Immune Response ◽

Innate Immunity ◽

Dendritic Cells ◽

Inflammatory Response ◽

Signaling Pathway ◽

Adhesion Molecule ◽

Immune Evasion ◽

Intercellular Adhesion Molecule ◽

Lectin Receptor

Intercellular adhesion molecule CD209 (DC-SIGN) is a membrane C-type lectin receptor expressed on the surface of dendritic cells and macrophages. CD209 plays an important role in innate immunity. Many studies have shown the possibility of interaction of the CD209 molecule with a number of dangerous pathogens of humans and animals. This review summarizes information on the structure of the CD209 gene and its product, describes the role of the CD209 protein in the immune response, in the migration of dendritic cells from the blood to the tissue, and their interaction with neutrophils. The currently known signaling pathway of activation through the CD209 inflammatory response is presented. The role of CD209 as an endocytic antigen receptor and the participation of the protein in immune evasion of pathogens are discussed. The mechanisms known to date for the development of infections caused by pathogens of various nature in animals are described.

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Interaction of Monocyte-Derived Dendritic Cells with Ara h 2 from Raw and Roasted Peanuts

Foods ◽

10.3390/foods9070863 ◽

2020 ◽

Vol 9 (7) ◽

pp. 863 ◽

Cited By ~ 2

Author(s):

Natalija Novak ◽

Soheila J. Maleki ◽

Carmen Cuadrado ◽

Jesus F. Crespo ◽

Beatriz Cabanillas

Keyword(s):

Dendritic Cells ◽

Human Monocyte ◽

Mannose Receptor ◽

Allergic Reactions ◽

Ara H 2 ◽

Allergenic Potential ◽

Sensitization Phase ◽

Mannose Receptors ◽

Dose Dependent

Ara h 2 is a relevant peanut allergen linked to severe allergic reactions. The interaction of Ara h 2 with components of the sensitization phase of food allergy (e.g., dendritic cells) has not been investigated, and could be key to understanding the allergenic potential of this allergen. In this study, we aimed to analyze such interactions and the possible mechanism involved. Ara h 2 was purified from two forms of peanut, raw and roasted, and labeled with a fluorescent dye. Human monocyte-derived dendritic cells (MDDCs) were obtained, and experiments of Ara h 2 internalization by MDDCs were carried out. The role of the mannose receptor in the internalization of Ara h 2 from raw and roasted peanuts was also investigated. Results showed that Ara h 2 internalization by MDDCs was both time and dose dependent. Mannose receptors in MDDCs had a greater implication in the internalization of Ara h 2 from roasted peanuts. However, this receptor was also important in the internalization of Ara h 2 from raw peanuts, as opposed to other allergens such as raw Ara h 3.

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