scholarly journals Myeloid and Plasmacytoid Dendritic Cells and Cancer – New Insights

2019 ◽  
Vol 7 (19) ◽  
pp. 3324-3340 ◽  
Author(s):  
Maya Gulubova ◽  
Koni Vancho Ivanova ◽  
Mehmed Hadzhi ◽  
Dimitur Chonov ◽  
Maria Magdalena Ignatova ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Cell Types ◽  
Tumour Microenvironment ◽  
Mhc I ◽  
Cross Presentation ◽  
Adaptive Immune ◽  
Histocompatibility Complex ◽  
T Helpers

Dendritic cells (DCs) use effective mechanisms to combat antigens and to bring about adaptive immune responses through their ability to stimulate nӓive T cells. At present, four major cell types are categorised as DCs: Classical or conventional (cDCs), Plasmacytoid (pDCs), Langerhans cells (LCs), and monocyte-derived DCs (Mo-DCs). It was suggested that pDCs, CD1c+ DCs and CD141+ DCs in humans are equivalent to mouse pDCs, CD11b+ DCs and CD8α+ DCs, respectively. Human CD141+ DCs compared to mouse CD8α+ DCs have remarkable functional and transcriptomic similarities. Characteristic markers, transcription factors, toll-like receptors, T helpers (Th) polarisation, cytokines, etc. of DCs are discussed in this review. Major histocompatibility complex (MHC) I and II antigen presentation, cross-presentation and Th polarisation are defined, and the dual role of DCs in the tumour is discussed. Human DCs are the main immune cells that orchestrate the immune response in the tumour microenvironment.

scholarly journals Crosstalk between Dendritic Cells and Immune Modulatory Agents against Sepsis

Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 323 ◽  
Author(s):  
Guoying Wang ◽  
Xianghui Li ◽  
Lei Zhang ◽  
Abualgasim Elgaili Abdalla ◽  
Tieshan Teng ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Critical Role ◽  
Innate Immune ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Th2 Responses ◽  
Novel Strategy

Dendritic cells (DCs) play a critical role in the immune system which sense pathogens and present their antigens to prime the adaptive immune responses. As the progression of sepsis occurs, DCs are capable of orchestrating the aberrant innate immune response by sustaining the Th1/Th2 responses that are essential for host survival. Hence, an in-depth understanding of the characteristics of DCs would have a beneficial effect in overcoming the obstacle occurring in sepsis. This paper focuses on the role of DCs in the progression of sepsis and we also discuss the reverse sepsis-induced immunosuppression through manipulating the DC function. In addition, we highlight some potent immunotherapies that could be used as a novel strategy in the early treatment of sepsis.

scholarly journals Recruitment of Rab27a to Phagosomes Controls Microbial Antigen Cross-Presentation by Dendritic Cells

2008 ◽  
Vol 76 (11) ◽  
pp. 5373-5380 ◽  
Author(s):  
Seong Hyun Kim ◽  
Annelies Visser ◽  
Carin Cruijsen ◽  
Adrianus W. M. van der Velden ◽  
Marianne Boes
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Antigen Processing ◽  
Small Gtpase ◽  
Complement C3 ◽  
Complement Components ◽  
Cross Presentation ◽  
Microbial Antigen ◽  
Protection Against Infection

ABSTRACT Polyreactive immunoglobulins (Ig) and complement components are present in tissues and blood of healthy individuals. They facilitate pathogen uptake and inactivation in lysosomes of phagocytes and thereby provide rapid protection against infection. Dendritic cells (DCs) are phagocytes that can acquire peptides from phagocytosed antigen to elicit cytotoxic immune responses by CD8+ T lymphocytes. The mechanisms that select peptides for cross-presentation are not fully resolved. Here we investigated the role of polyreactive Ig and complement in directing phagosomal antigen processing for cross-presentation. Phagocytosis facilitated by serum opsonization required the presence of Ig for effective antigen cross-presentation of microbe-derived antigen. The presence of complement C3 in serum promoted phagocytosis, yet phagosomes were defective in antigen degradation. The small GTPase Rab27a was recently implicated in antigen cross-presentation and was rapidly recruited to phagosomes only when Ig was present. Our data suggest that prebinding of antigen by polyreactive Ig potentiates the efficiency of antigen cross-presentation to CD8+ T cells through recruitment of Rab27a.

scholarly journals MicroRNA target Fc receptors to regulate Ab-dependent Ag uptake in primary macrophages and dendritic cells

2016 ◽  
Vol 22 (7) ◽  
pp. 510-521 ◽  
Author(s):  
Afsar Raza Naqvi ◽  
Jezrom B Fordham ◽  
Salvador Nares
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Innate Immune Responses ◽  
Microrna Target ◽  
Adaptive Immune ◽  
Latex Beads ◽  
Tnf Α ◽  
Particle Internalization ◽  
Pro Inflammatory Cytokines

Phagocytosis commences with particle internalization and culminates with the activation of innate and adaptive immune responses. However, the role of miRNAs in phagocytosis remains largely unknown. In this study, we examined the role of miR-24, miR-30b and miR-142-3p in Ab Fc receptor (FcR)-mediated phagocytosis by macrophages (MΦ) and dendritic cells (DC). The expression of these miRNAs was reduced following phagocytosis of both IgG-opsonized beads and Escherichia coli, indicating their regulatory role in the process. Further, overexpression of these miRNAs impaired the uptake of IgG-coated latex beads, which corroborated the reduced secretion of the pro-inflammatory cytokines TNF-α and IL-8 and down-regulation of PKC-α, as well as superoxide-generating enzyme NADPH oxidase 2 expression level. Mechanistically, MΦ and DC transfected with miRNA mimics show marked reduction in expression of FcRs including FCGR2A, FcɛR1G and FCER2. We show that FcɛR1G expression is not affected at the transcription level, rather it is post-transcriptionally regulated by miR-30b. Finally, we demonstrate that siRNA-mediated knockdown of FcɛR1G leads to reduced uptake of IgG-opsonized beads, indicating its involvement on Ab-mediated phagocytosis. These results uncover miR-24, miR-30b and miR-142-3p as an essential component of FcR-mediated phagocytosis and associated innate immune responses.

Lack of endogenous TRIM5α-mediated restriction in rhesus macaque dendritic cells

Blood ◽  
2008 ◽  
Vol 112 (9) ◽  
pp. 3772-3776 ◽  
Author(s):  
Nathalie J. Arhel ◽  
Sébastien Nisole ◽  
Laetitia Carthagena ◽  
Frédéric Coutant ◽  
Philippe Souque ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Rhesus Macaque ◽  
Rhesus Macaques ◽  
Cell Types ◽  
Primary Cells ◽  
Adaptive Immune ◽  
Trim Protein ◽  
Tripartite Motif ◽  
Hiv 1

Rhesus macaques are resistant to infection by HIV-1 as a result of an innate cellular restriction mechanism attributable to the expression of rhTRIM5α, a member of the large tripartite motif (TRIM) protein family. TRIM5α-mediated restriction, which occurs before reverse transcription through targeting of the HIV-1 capsid, has been identified in a number of macaque primary cells and cell lines and is thought to occur in all macaque cell types. We report, however, that rhesus macaque dendritic cells (DCs) lack TRIM5α-mediated restriction and are equally permissive to HIV-1 infection as human DCs. Evidence suggests that, although TRIM5α RNA levels are normal in these cells, the protein may be dysfunctional. We propose that abrogation of TRIM5α-mediated restriction in DCs, although still operative in cells that replicate HIV-1 (macrophages, T lymphocytes), illustrates the need for innate mechanisms to not inhibit adaptive immune responses to ensure an optimal fight against pathogens.

scholarly journals Distinct mechanisms of neonatal tolerance induced by dendritic cells and thymic B cells.

1991 ◽  
Vol 173 (3) ◽  
pp. 549-559 ◽  
Author(s):  
M Inaba ◽  
K Inaba ◽  
M Hosono ◽  
T Kumamoto ◽  
T Ishida ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
B Cells ◽  
Cell Types ◽  
Cell Sorter ◽  
Histocompatibility Complex ◽  
Different Types ◽  
Induced Tolerance ◽  
Antigen Presenting

To assess the role of different types of antigen-presenting cells (APC) in the induction of tolerance, we isolated B cells, macrophages, and dendritic cells from thymus and spleen, and injected these into neonatal BALB/c mice across an Mls-1 antigenic barrier. One week after injection of APC from Mls-1-incompatible mice or from control syngeneic mice, we measured the number of thymic, Mls-1a-reactive, V beta 6+ T cells and the capacity of thymocytes to induce a graft-vs.-host (GVH) reaction in popliteal lymph nodes of Mls-1a mice. Injection of thymic but not spleen B cells deleted thymic, Mls-1a-reactive V beta 6+ T cells and induced tolerance in the GVH assay. The thymic B cells were primarily of the CD5+ type, and fluorescence-activated cell sorter-purified CD5+ thymic B cells were active. Injection of dendritic cells from spleen or thymus also induced tolerance, but the V beta 6 cells were anergized rather than deleted. Macrophages from thymus did not induce tolerance. Dendritic cells and thymic B cells were also effective in inducing tolerance even when injected into Mls-, major histocompatibility complex-incompatible, I-E- mice, but only thymic B cells depleted V beta 6-expressing T cells. Therefore, different types of bone marrow-derived APC have different capacities for inducing tolerance, and the active cell types (dendritic cells and CD5+ thymic B cells) can act by distinct mechanisms.

scholarly journals Cancer Acidity and Hypertonicity Contribute to Dysfunction of Tumor-Associated Dendritic Cells: Potential Impact on Antigen Cross-Presentation Machinery

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2403
Author(s):  
Sven Burgdorf ◽  
Stefan Porubsky ◽  
Alexander Marx ◽  
Zoran V. Popovic
Keyword(s):  
Dendritic Cells ◽  
Immune Escape ◽  
Cell Types ◽  
Mononuclear Phagocyte ◽  
Scientific Data ◽  
Neoplastic Tissue ◽  
Antigen Uptake ◽  
Mhc I ◽  
Cross Presentation ◽  
Extracellular Matrix Components

Macrophages (MΦ) and dendritic cells (DC), major players of the mononuclear phagocyte system (MoPh), are potent antigen presenting cells that steadily sense and respond to signals from the surrounding microenvironment, leading to either immunogenic or tolerogenic outcomes. Next to classical MHC-I/MHC-II antigen-presentation pathways described in the vast majority of cell types, a subset of MoPh (CD8+, XCR1+, CLEC9A+, BDCA3+ conventional DCs in human) is endowed with a high competence to cross-present external (engulfed) antigens on MHC-I molecules to CD8+ T-cells. This exceptional DC function is thought to be a crucial crossroad in cytotoxic antitumor immunity and has been extensively studied in the past decades. Biophysical and biochemical fingerprints of tumor micromilieus show significant spatiotemporal differences in comparison to non-neoplastic tissue. In tumors, low pH (mainly due to extracellular lactate accumulation via the Warburg effect and via glutaminolysis) and high oncotic and osmotic pressure (resulting from tumor debris, increased extracellular matrix components but in part also triggered by nutritive aspects) are—despite fluctuations and difficulties in measurement—likely the most constant general hallmarks of tumor microenvironment. Here, we focus on the influence of acidic and hypertonic micromilieu on the capacity of DCs to cross-present tumor-specific antigens. We discuss complex and in part controversial scientific data on the interference of these factors with to date reported mechanisms of antigen uptake, processing and cross-presentation, and we highlight their potential role in cancer immune escape and poor clinical response to DC vaccines.

scholarly journals Non-canonical autophagy in dendritic cells restricts cross-presentation and anti-tumor immunity

2019 ◽  
Author(s):  
Payel Sil ◽  
Fei Zhao ◽  
Ginger W. Muse ◽  
Sing-Wai Wong ◽  
Joseph P. Kolb ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Molecular Mechanisms ◽  
Tumor Therapy ◽  
Tumor Burden ◽  
Mhc I ◽  
Cross Presentation ◽  
Cell Responses ◽  
Histocompatibility Complex ◽  
Novel Strategy ◽  
Gain Access

SummaryMajor Histocompatibility Complex I (MHC-I) molecules classically present peptides derived from endogenous antigens, but exogenous antigens can also gain access to the MHC-I machinery in dendritic cells (DCs), which can activate antigen-specific CD8+T cells. This process, termed cross-presentation, can be triggered by the uptake of dying autologous cells, including tumor cells, by DCs. The molecular mechanisms that underlie efficient cross-presentation remain largely uncharacterized, and an improved understanding of these mechanisms might reveal novel strategies for anti-tumor therapies. Rubicon (RUBCN) is a molecule required for LC3-associated phagocytosis (LAP), but dispensable for canonical autophagy, and mice lacking this protein develop an autoimmune inflammatory pathology with age. Here, we demonstrate thatRubcn-deficient DCs have increased retention of engulfed cellular cargo in immature phagosomes resulting in increased phagosome-to-cytosol escape and antigen access to proteasome-mediated degradation. As a result, mice selectively lackingRubcnin DCs mount stronger tumor antigen-specific CD8+T cell responses and exhibit decreased tumor burden compared to wild type littermates. These findings identify LAP as a key regulator of cross-presentation and suggest that targeting RUBCN might represent a novel strategy for anti-tumor therapy.

scholarly journals Classical dendritic cells as a unique immune cell lineage

2012 ◽  
Vol 209 (6) ◽  
pp. 1053-1056 ◽  
Author(s):  
Boris Reizis
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Immune Cell ◽  
Critical Role ◽  
Cell Lineage ◽  
Specific Pattern ◽  
Adaptive Immune ◽  
Definition Of

Despite the critical role of classical dendritic cells (cDCs) in the initiation of adaptive immune responses, the genetic and phenotypic definition of cDCs remains moot. Two new studies designate Zbtb46 as a novel transcription factor that is specifically expressed in all cDCs in both humans and mice. Although Zbtb46 appears dispensable for cDC development, its specific pattern of expression supports the notion that cDCs constitute a unique immune cell lineage. Furthermore, these two studies provide novel tools that will aid in the study of cDC progenitors, visualization of cDCs in vivo, and depletion of cDCs for functional analysis.

scholarly journals Interaction of severe acute respiratory syndrome-associated coronavirus with dendritic cells

2006 ◽  
Vol 87 (7) ◽  
pp. 1953-1960 ◽  
Author(s):  
Martin Spiegel ◽  
Kerstin Schneider ◽  
Friedemann Weber ◽  
Manfred Weidmann ◽  
Frank T. Hufert
Keyword(s):  
Dendritic Cells ◽  
Severe Acute Respiratory Syndrome ◽  
Immune Responses ◽  
Rt Pcr ◽  
Immunofluorescence Analysis ◽  
Adaptive Immune ◽  
Surface Marker Expression ◽  
Histocompatibility Complex ◽  
Novel Coronavirus ◽  
Adaptive Immune Systems

Severe acute respiratory syndrome (SARS) of humans is caused by a novel coronavirus of zoonotic origin termed SARS-associated coronavirus (SARS-CoV). The virus induces severe injury of lung tissue, as well as lymphopenia and destruction of the architecture of lymphatic tissue by as-yet-unknown mechanisms. In this study, the interaction of SARS-CoV with dendritic cells (DCs), the key regulators of immune responses, was analysed. Monocyte-derived DCs were infected with SARS-CoV and analysed for viability, surface-marker expression and alpha interferon (IFN-α) induction. SARS-CoV infection was monitored by quantitative RT-PCR, immunofluorescence analysis and recovery experiments. SARS-CoV infected both immature and mature DCs, although replication efficiency was low. Immature DCs were activated by SARS-CoV infection and by UV-inactivated SARS-CoV. Infected DCs were still viable on day 6 post-infection, but major histocompatibility complex class I upregulation was missing, indicating that DC function was impaired. Additionally, SARS-CoV infection induced a delayed activation of IFN-α expression. Therefore, it is concluded that SARS-CoV has the ability to circumvent both the innate and the adaptive immune systems.

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