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 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 The role of cDC1s in vivo: CD8 T cell priming through cross-presentation

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 98 ◽  
Author(s):  
Derek Theisen ◽  
Kenneth Murphy
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
T Cell ◽  
Antigen Processing ◽  
Molecular Mechanisms ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cross Presentation ◽  
Cell Responses

The cDC1 subset of classical dendritic cells is specialized for priming CD8 T cell responses through the process of cross-presentation. The molecular mechanisms of cross-presentation remain incompletely understood because of limited biochemical analysis of rare cDC1 cells, difficulty in their genetic manipulation, and reliance onin vitrosystems based on monocyte- and bone-marrow-derived dendritic cells. This review will discuss cross-presentation from the perspective of studies with monocyte- or bone-marrow-derived dendritic cells while highlighting the need for future work examining cDC1 cells. We then discuss the role of cDC1s as a cellular platform to combine antigen processing for class I and class II MHC presentation to allow the integration of “help” from CD4 T cells during priming of CD8 T cell responses.

scholarly journals SNX17 regulates antigen internalization and phagosomal maturation by dendritic cells

2021 ◽  
Author(s):  
Ignacio Cebrian ◽  
Sofía Dinamarca ◽  
Cristina Croce ◽  
Anna Salvioni ◽  
Facundo Garrido ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Mhc Class I ◽  
Fluid Phase ◽  
Antigenic Peptides ◽  
Sorting Nexin ◽  
Cross Presentation ◽  
Phagosomal Maturation ◽  
Fluid Phase Endocytosis

Abstract Cross-presentation is the process whereby antigenic peptides derived from exogenous antigens are associated to MHC class I molecules triggering the activation of CD8+ T lymphocytes. The endocytic route of dendritic cells (DCs) is strongly specialized to achieve antigen cross-presentation efficiently, which is crucial to initiate cytotoxic immune responses against many pathogens (i.e. Toxoplasma gondii) and tumors. Nevertheless, the endosomal molecular effectors involved in this process are not completely understood. In particular, the role of sorting nexin (SNX) proteins in cross-presentation has never been addressed. In this work, we identify the endosomal protein SNX17 as a key regulator of antigen internalization and cross-presentation by DCs. Our results demonstrate that SNX17 expression in DCs is essential to guarantee a normal cross-presentation of soluble, particulate and T. gondii-associated antigens. The silencing of SNX17 expression in DCs significantly affected the uptake of exogenous antigens by fluid-phase endocytosis and phagocytosis, but not by receptor-mediated endocytosis. Moreover, the knock-down of SNX17 impaired T. gondii invasion, CD11b integrin recycling and hampered the organization of the actin cytoskeleton. Finally, we show that SNX17 controls the proper maturation of DC phagosomes. Our findings provide compelling evidence that SNX17 plays a central role in the modulation of DC endocytic network, which is crucial for competent antigen internalization and cross-presentation.

scholarly journals Cancer Stem Cells Are Possible Key Players in Regulating Anti-Tumor Immune Responses: The Role of Immunomodulating Molecules and MicroRNAs

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1674
Author(s):  
Sara Tomei ◽  
Ola Ibnaof ◽  
Shilpa Ravindran ◽  
Soldano Ferrone ◽  
Cristina Maccalli
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Immune Responses ◽  
Antigen Processing ◽  
Aberrant Expression ◽  
Immunological Profile ◽  
Malignant Lesions ◽  
Novel Therapeutic Strategies ◽  
Antigen Processing And Presentation

Cancer cells endowed with stemness properties and representing a rare population of cells within malignant lesions have been isolated from tumors with different histological origins. These cells, denominated as cancer stem cells (CSCs) or cancer initiating cells (CICs), are responsible for tumor initiation, progression and resistance to therapies, including immunotherapy. The dynamic crosstalk of CSCs/CICs with the tumor microenvironment orchestrates their fate and plasticity as well as their immunogenicity. CSCs/CICs, as observed in multiple studies, display either the aberrant expression of immunomodulatory molecules or suboptimal levels of molecules involved in antigen processing and presentation, leading to immune evasion. MicroRNAs (miRNAs) that can regulate either stemness properties or their immunological profile, with in some cases dual functions, can provide insights into these mechanisms and possible interventions to develop novel therapeutic strategies targeting CSCs/CICs and reverting their immunogenicity. In this review, we provide an overview of the immunoregulatory features of CSCs/CICs including miRNA profiles involved in the regulation of the interplay between stemness and immunological properties.

scholarly journals A Missing Link: Engagements of Dendritic Cells in the Pathogenesis of SARS-CoV-2 Infections

2021 ◽  
Vol 22 (3) ◽  
pp. 1118
Author(s):  
Abdulaziz Alamri ◽  
Derek Fisk ◽  
Deepak Upreti ◽  
Sam K. P. Kung
Keyword(s):  
Dendritic Cells ◽  
Severe Acute Respiratory Syndrome ◽  
Immune Responses ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Viral Disease ◽  
Cell Recruitment ◽  
Cross Presentation ◽  
Cell Immunity ◽  
Immune Cell Recruitment

Dendritic cells (DC) connect the innate and adaptive arms of the immune system and carry out numerous roles that are significant in the context of viral disease. Their functions include the control of inflammatory responses, the promotion of tolerance, cross-presentation, immune cell recruitment and the production of antiviral cytokines. Based primarily on the available literature that characterizes the behaviour of many DC subsets during Severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19), we speculated possible mechanisms through which DC could contribute to COVID-19 immune responses, such as dissemination of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to lymph nodes, mounting dysfunctional inteferon responses and T cell immunity in patients. We highlighted gaps of knowledge in our understanding of DC in COVID-19 pathogenesis and discussed current pre-clinical development of therapies for COVID-19.

scholarly journals Rho-mDia1 pathway is required for adhesion, migration, and T-cell stimulation in dendritic cells

Blood ◽  
2010 ◽  
Vol 116 (26) ◽  
pp. 5875-5884 ◽  
Author(s):  
Hideaki Tanizaki ◽  
Gyohei Egawa ◽  
Kayo Inaba ◽  
Tetsuya Honda ◽  
Saeko Nakajima ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
T Cell ◽  
Immune Responses ◽  
Lymph Nodes ◽  
Actin Polymerization ◽  
Cell Stimulation ◽  
T Cell Stimulation ◽  
Acquired Immune Responses

Abstract Dendritic cells (DCs) are essential for the initiation of acquired immune responses through antigen acquisition, migration, maturation, and T-cell stimulation. One of the critical mechanisms in this response is the process actin nucleation and polymerization, which is mediated by several groups of proteins, including mammalian Diaphanous-related formins (mDia). However, the role of mDia in DCs remains unknown. Herein, we examined the role of mDia1 (one of the isoforms of mDia) in DCs. Although the proliferation and maturation of bone marrow-derived DCs were comparable between control C57BL/6 and mDia1-deficient (mDia1−/−) mice, adhesion and spreading to cellular matrix were impaired in mDia1−/− bone marrow–derived DCs. In addition, fluorescein isothiocyanate-induced cutaneous DC migration to draining lymph nodes in vivo and invasive migration and directional migration to CCL21 in vitro were suppressed in mDia1−/− DCs. Moreover, sustained T-cell interaction and T-cell stimulation in lymph nodes were impaired by mDia1 deficiency. Consistent with this, the DC-dependent delayed hypersensitivity response was attenuated by mDia1-deficient DCs. These results suggest that actin polymerization, which is mediated by mDia1, is essential for several aspects of DC-initiated acquired immune responses.

scholarly journals Dendritic cells play no significant role in the laser-induced choroidal neovascularization model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Steven Droho ◽  
Harris Perlman ◽  
Jeremy A. Lavine
Keyword(s):  
Dendritic Cells ◽  
Steady State ◽  
Choroidal Neovascularization ◽  
Significant Role ◽  
Age Related Macular Degeneration ◽  
Complement Components ◽  
Innate And Adaptive Immunity ◽  
Laser Injury ◽  
Age Related

AbstractAge-related macular degeneration (AMD) is genetically associated with complement. Dendritic cells (DCs) play key roles during innate and adaptive immunity, and express complement components and their receptors. We investigated ocular DC heterogeneity and the role of DCs in the laser-induced choroidal neovascularization (CNV) model. In order to determine the function of DCs, we used two models of DC deficiency: the Flt3−/− and Flt3l−/− mouse. We identified three types of ocular DCs: plasmacytoid DC, classical DC-1, and classical DC-2. At steady-state, classical DCs were found in the iris and choroid but were not detectable in the retina. Plasmacytoid DCs existed at very low levels in iris, choroid, and retina. After laser injury, the number of each DC subset was up-regulated in the choroid and retina. In Flt3−/− mice, we found reduced numbers of classical DCs at steady-state, but each DC subset equally increased after laser injury between wildtype and Flt3−/− mice. In Flt3l−/− mice, each DC subsets was severely reduced after laser injury. Neither Flt3−/− or Flt3l−/− mice demonstrated reduced CNV area compared to wildtype mice. DCs do not play any significant role during the laser-induced CNV model of neovascular AMD.

scholarly journals P01.11 Role of exosomes as promotors or biomarkers to study activation of leukemia-derived dendritic cells (DCleu)-mediated antileukemic activation of adaptive and innate immune-reactive cells against AML-blasts

2020 ◽  
Vol 8 (Suppl 2) ◽  
pp. A13.2-A14
Author(s):  
L Li ◽  
V Mussack ◽  
E Pepeldjiyska ◽  
A Hartz ◽  
A Rank ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Healthy Volunteers ◽  
Information Transfer ◽  
Immune Monitoring ◽  
Lymphocyte Culture ◽  
Innate Immune ◽  
Proliferating Cells ◽  
Continuous Increase

BackgroundAntileukemic responses of immune reactive cells in AML-patients need to be improved. Combinations of blast-modulatory kitM (GM-CSF+PGE1) (vs control) convert myeloid blasts into dendritic cells of leukemic origin (DCleu), that effectively activate immune-cells against leukemic blasts. Exosomes are small (30–150 nm) membranous vesicles of endocytic origin produced by all cells under physiological and pathological conditions. Their involvement in nearly all aspects of malignant transformation has generated much interest in their biology, mechanisms responsible for information transfer and their role in immune-surveillance as well as -escape.Exosomes secreted by dendritic cells (DCs) have been shown to allow efficient activation of T lymphocytes, displaying potential as promoters of adaptive immune responses.Materials and Methods1)DC/DCleu-culture of blast containing AML patients’ whole blood (WB) (n=10) and of healthy volunteers(n=8) with kits, T-cell enriched mixed lymphocyte culture (MLC) with kit- vs un-treated WB, functional blast-cytotoxicity and, leukemia-specificity assays (Degranulation/intracellular cytokine-assays), Flowcytometric evaluation of blast-,DC- and lymphocyte composition before or after cultures. 2)Exosomes were isolated by immunoaffinity from serum, DC- and MLC-culture supernatants of 3 AML patients and 3 healthy volunteers. Exosomes were negatively stained and characterized by transmission electron microscopy (TEM). Fluorescence nanoparticle tracking analysis (fNTA) was performed to determine exosomal size and -concentration. Obtained results were compared in AML and healthy volunteers.ResultsAddition of kitM to blast-containing WB significantly increased frequencies of mature DC/DCleu and their subtypes compared to untreated WB without induction of blasts’ proliferation. Immune monitoring showed a continuous increase ofactivated/proliferating cells of the adaptive and innate immune system after Tcell-enriched MLC using kitM pretreated vs -untreated WB, suggesting a production/activation of (potentially leukemia-specific) cells after kit-stimulation. Moreover kit-pretreated WB regularly and significantly improved provision, activation as well as antileukemic and leukemia-specifically directed immune reactive cells after MLC. TEM showed exosome-like structures with a typically cup-shaped appearance without any differences between healthy and AML samples. fNTA revealed average vesicle sizes of 177±23 nm (healthy) and 178±17 nm (AML). Higher levels of EVs were detectable in AML samples compared to healthy controls in serum and after DC-culture, but lower levels after MLC independent of culture conditions.Interestingly, the number of EVs increased during cultivation of DC of AML and healthy samples, but not in AML-derived MLC samples.ConclusionsWe will provide data in AML patients and healthy volunteers about a potential role of DCs- and MLC-derived exosomes as biomarkers in immune responses, malignant progression or as potential therapeutic targets for AML patients.Disclosure InformationL. li: None. V. Mussack: None. E. Pepeldjiyska: None. A. Hartz: None. A. Rank: None. C. Schmid: None. E. Özkaya: None. S. Ugur: None. M. Pfaffl: None. H. Schmetzer: None.

scholarly journals A simple self-adjuvanting biomimetic nanovaccine self-assembled with the conjugate of phospholipids and nucleotides can induce a strong cancer immunotherapeutic effect

2021 ◽  
Vol 9 (1) ◽  
pp. 84-92
Author(s):  
Dan Liu ◽  
Jiale Liu ◽  
Bing Ma ◽  
Bo Deng ◽  
Xigang Leng ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Immune Responses ◽  
T Cell Responses ◽  
Cpg Odn ◽  
Cross Presentation ◽  
Cell Responses ◽  
Self Assembled ◽  
Cancer Immunotherapeutic

The biomimetic nanovaccines not only promoted antigens endocytosis into dendritic cells via receptor-mediated pathways but also induced antigens cross-presentation eliciting CD8+ T-cell responses. CPG-ODN as an adjuvant further enhanced the anti-tumor immune responses.

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