The influence of the co-monomer ratio of poly[acrylonitrile-co-(N-vinylpyrrolidone)]s on primary human monocyte-derived dendritic cells

2013 ◽  
Vol 1569 ◽  
pp. 21-26 ◽  
Author(s):  
Toralf Roch ◽  
Marc Behl ◽  
Michael Zierke ◽  
Benjamin F. Pierce ◽  
Karl Kratz ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Cellular Response ◽  
Chemical Properties ◽  
Human Monocyte ◽  
Cellular Responses ◽  
Inflammatory Conditions ◽  
Primary Monocyte ◽  
Poly Acrylonitrile ◽  
Activation Status

ABSTRACTA major goal in the field of regenerative medicine is to improve our understanding of how biomaterial properties affect cells of the immune system. Systematic variation of defined chemical properties could help to understand which factors determine and modulate cellular responses. A series of copolymers poly[acrylonitrile-co-(N-vinylpyrrolidone)]s (P(AN-co-NVP)) served as model system, in which increasing hydrophilicity was adjusted by increasing the content related to the NVP based repeating units (nNVP) (0, 4.6, 11.8, 22.3, and 29.4 mol%). The influence of increasing nNVPcontents on cellular response of human primary monocyte derived dendritic cells (DC), which play a key role in the initiation of immune responses, was investigated. It was shown using the LAL-Test as well as a macrophage-based assay, that the materials were free of endotoxins and other microbial contaminations, which could otherwise bias the readout of the DC experiments. The increasing nNVPcontent led to a slightly increased cell death of DC, whereas the activation status of DC was not systematically altered by the different P(AN-co-NVP)s as demonstrated by the expression of co-stimulatory molecule and cytokine secretion. Similarly, under inflammatory conditions mimicked by the addition of lipopolysaccharides (LPS), neither the expression of co-stimulatory molecules nor the release of cytokines was influenced by the different copolymers. Conclusively, our data showed that this class of copolymers does not substantially influence the viability and the activation status of DC.

scholarly journals CRISPR-based functional genomics in human dendritic cells

2020 ◽  
Author(s):  
Marco Jost ◽  
Amy N. Jacobson ◽  
Jeffrey A. Hussmann ◽  
Giana Cirolia ◽  
Michael A. Fischbach ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Genome Editing ◽  
Individual Variation ◽  
Human Microbiome ◽  
Human Monocyte ◽  
Genetic Screens ◽  
Mucosal Surfaces ◽  
Immune Phenotypes ◽  
Human Dendritic Cells

AbstractDendritic cells (DCs) regulate processes ranging from antitumor and antiviral immunity to host-microbe communication at mucosal surfaces. It remains difficult, however, to genetically manipulate human DCs, limiting our ability to probe how DCs elicit specific immune responses. Here, we develop a CRISPR/Cas9 genome editing method for human monocyte-derived DCs (moDCs) that mediates knockouts with a median efficiency of >93% across >300 genes. Using this method, we perform genetic screens in moDCs, identifying mechanisms by which DCs tune responses to lipopolysaccharides from the human microbiome. In addition, we reveal donor-specific responses to lipopolysaccharides, underscoring the importance of assessing immune phenotypes in donor-derived cells, and identify genes that control this specificity, highlighting the potential of our method to pinpoint determinants of inter-individual variation in immune responses. Our work sets the stage for a systematic dissection of the immune signaling at the host-microbiome interface and for targeted engineering of DCs for neoantigen vaccination.

scholarly journals IN LABORATORY GENERATION AND MATURATION OF HUMAN MONOCYTE-DERIVED DENDRITIC CELLS FOR CANCER IMMUNOTHERAPY

2020 ◽  
pp. 46-52
Author(s):  
KANCHAN K. MISHRA ◽  
SUMIT BHARADVA ◽  
MEGHNAD G. JOSHI ◽  
ARVIND GULBAKE
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Gradient Centrifugation ◽  
Critical Role ◽  
Human Monocyte ◽  
Blood Monocytes ◽  
Adaptive Immune ◽  
Immunodeficiency Virus ◽  
Adaptive Immune Systems

Dendritic cells (DCs) play a critical role in the regulation of adaptive immune responses, furthermore they act as a bridge between the innate and the adaptive immune systems they have been ideal candidates for cell-based immunotherapy of cancers and infections in humans. The first reported trial using DCs in 1995, since they have been used in trials all over the world for several of indications, including cancer and human immunodeficiency virus infection. Generally, for in vitro experiments or for DCs vaccination monocyte-derived dendritic cells (moDCs) were generated from purified monocytes that isolated from peripheral blood by density gradient centrifugation. A variety of methods can be used for enrichment of monocytes for generation of clinical-grade DCs. Herein we summarized up to date understanding of systems and inputs used in procedures to differentiate DCs from blood monocytes in vitro.

scholarly journals Human Dendritic Cells: Ontogeny and Their Subsets in Health and Disease

2018 ◽  
Vol 6 (4) ◽  
pp. 88 ◽  
Author(s):  
Sandra Solano-Gálvez ◽  
Sonia Tovar-Torres ◽  
María Tron-Gómez ◽  
Ariane Weiser-Smeke ◽  
Diego Álvarez-Hernández ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
Current Knowledge ◽  
Lymphoid Organ ◽  
Heterogeneous Population ◽  
Health And Disease ◽  
Human Dendritic Cells ◽  
Activation Status

Dendritic cells (DCs) are a type of cells derived from bone marrow that represent 1% or less of the total hematopoietic cells of any lymphoid organ or of the total cell count of the blood or epithelia. Dendritic cells comprise a heterogeneous population of cells localized in different tissues where they act as sentinels continuously capturing antigens to present them to T cells. Dendritic cells are uniquely capable of attracting and activating naïve CD4+ and CD8+ T cells to initiate and modulate primary immune responses. They have the ability to coordinate tolerance or immunity depending on their activation status, which is why they are also considered as the orchestrating cells of the immune response. The purpose of this review is to provide a general overview of the current knowledge on ontogeny and subsets of human dendritic cells as well as their function and different biological roles.

scholarly journals Intranasal Vaccination with the Recombinant Listeria monocytogenes ΔactA prfA*Mutant Elicits Robust Systemic and Pulmonary Cellular Responses and Secretory Mucosal IgA

2011 ◽  
Vol 18 (4) ◽  
pp. 640-646 ◽  
Author(s):  
Jin Qiu ◽  
Lin Yan ◽  
Jianbo Chen ◽  
Crystal Y. Chen ◽  
Ling Shen ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Immune Responses ◽  
Cellular Response ◽  
Cellular Responses ◽  
Broth Culture ◽  
Intravenous Route ◽  
Content Type ◽  
Vaccine Candidates ◽  
Ifn Γ ◽  
Subcutaneous Immunization

ABSTRACTWe previously showed that recombinant (r)Listeria monocytogenescarrying ΔactAand a selectedprfA*mutation (r-ListeriaΔactA prfA*) secreted >100-fold more immunogen in broth culture than wild-type r-Listeriaor r-ListeriaΔactAand elicited much greater cellular and humoral immune responses than r-ListeriaΔactAafter intravenous vaccination of mice. Here, we conducted comparative studies evaluating vaccine-elicited immune responses in systemic and mucosal sites after intranasal, intravenous, intraperitoneal, or subcutaneous immunization of mice with r-ListeriaΔactA prfA*vaccine candidates. Intranasal vaccination of mice with r-ListeriaΔactA prfA* vaccine candidates elicited a robust gamma interferon-positive (IFN-γ+) cellular response in systemic sites, although intravenous or intraperitoneal immunization was more efficient. Surprisingly, intranasal vaccination elicited an appreciable pulmonary IFN-γ+cellular response that was nonstatistically higher than the magnitude induced by the intravenous route but was significantly greater than that elicited by subcutaneous immunization. Furthermore, although intranasal r-ListeriaΔactA prfA*delivery induced poor systemic IgG responses, intranasal vaccination elicited appreciable secretory immunogen-specific IgA titers that were similar to or higher in mucosal fluid than those induced by subcutaneous and intravenous immunizations. Thus, intranasal vaccination with r-ListeriaΔactA prfA*appears to be a useful approach for eliciting robust systemic and pulmonary cellular responses and measurable secretory mucosal IgA titers.

scholarly journals Induction of immune tolerance to FIX by intramuscular AAV gene transfer is independent of the activation status of dendritic cells

Blood ◽  
2010 ◽  
Vol 115 (3) ◽  
pp. 500-509 ◽  
Author(s):  
Arpita S. Bharadwaj ◽  
Meagan Kelly ◽  
Dongsoo Kim ◽  
Hengjun Chao
Keyword(s):  
Dendritic Cells ◽  
Gene Transfer ◽  
Immune Responses ◽  
Immune Tolerance ◽  
Intramuscular Injection ◽  
Viral Vectors ◽  
Critical Role ◽  
Host Immune System ◽  
Efficient Induction ◽  
Activation Status

Abstract The nature of viral vectors is suggested to be a significant contributor to undesirable immune responses subsequent to gene transfer. Such viral vectors, recognized as danger signals by the host immune system, activate dendritic cells (DCs), causing unwanted antivector and/or transgene product immunity. We recently reported efficient induction of immune tolerance to coagulation factor IX (FIX) by direct intramuscular injection of adeno-associated virus (AAV)–FIX. AAV vectors are nonpathogenic and elicit minimal inflammatory response. We hypothesized that the nonpathogenic nature of AAV plays a critical role in induction of tolerance after AAV gene transfer. We observed inefficient recruitment and activation of DCs subsequent to intramuscular injection of AAV. To further validate our hypothesis, we examined immune responses to FIX after intramuscular injection of AAV with simultaneous activation of DCs. We were able to achieve phenotypic and functional activation of DCs after administration of lipopolysaccharide and anti-CD40 antibody. However, we observed efficient induction of FIX tolerance irrespective of DC activation in mice with different genetic and major histocompatibility complex backgrounds. Furthermore, activation of DCs did not exaggerate the immune response induced after intramuscular injection of AAV serotype 2 vector. Our results demonstrate that induction of FIX tolerance after AAV gene transfer is independent of DC activation status.

scholarly journals Severe Acute Respiratory Syndrome Coronavirus Fails To Activate Cytokine-Mediated Innate Immune Responses in Cultured Human Monocyte-Derived Dendritic Cells

2005 ◽  
Vol 79 (21) ◽  
pp. 13800-13805 ◽  
Author(s):  
Thedi Ziegler ◽  
Sampsa Matikainen ◽  
Esa Rönkkö ◽  
Pamela Österlund ◽  
Maarit Sillanpää ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Severe Acute Respiratory Syndrome ◽  
Immune Responses ◽  
A549 Cells ◽  
Human Monocyte ◽  
Innate Immune ◽  
Lung Epithelial Cells ◽  
Cytokine Gene Expression ◽  
Innate Immune Responses ◽  
Necrosis Factor Alpha

ABSTRACT Activation of host innate immune responses was studied in severe acute respiratory syndrome coronavirus (SCV)-infected human A549 lung epithelial cells, macrophages, and dendritic cells (DCs). In all cell types, SCV-specific subgenomic mRNAs were seen, whereas no expression of SCV proteins was found. No induction of cytokine genes (alpha interferon [IFN-α], IFN-β, interleukin-28A/B [IL-28A/B], IL-29, tumor necrosis factor alpha, CCL5, or CXCL10) or IFN-α/β-induced MxA gene was seen in SCV-infected A549 cells, macrophages, or DCs. SCV also failed to induce DC maturation (CD86 expression) or enhance major histocompatibility complex class II expression. Our data strongly suggest that SCV fails to activate host cell cytokine gene expression in human macrophages and DCs.

scholarly journals Immune responses of macrophages and dendritic cells regulated by mTOR signalling

2013 ◽  
Vol 41 (4) ◽  
pp. 927-933 ◽  
Author(s):  
Karl Katholnig ◽  
Monika Linke ◽  
Ha Pham ◽  
Markus Hengstschläger ◽  
Thomas Weichhart
Keyword(s):  
Dendritic Cells ◽  
Immune System ◽  
Immune Responses ◽  
Inflammatory Mediators ◽  
Cellular Response ◽  
Mtor Pathway ◽  
The Body ◽  
Innate Immune ◽  
Immune Functions ◽  
Tissue Remodelling

The innate myeloid immune system is a complex network of cells that protect against disease by identifying and killing pathogens and tumour cells, but it is also implicated in homoeostatic mechanisms such as tissue remodelling and wound healing. Myeloid phagocytes such as monocytes, macrophages or dendritic cells are at the basis of controlling these immune responses in all tissues of the body. In the present review, we summarize recent studies demonstrating that mTOR [mammalian (or mechanistic) target of rapamycin] regulates innate immune reactions in macrophages and dendritic cells. The mTOR pathway serves as a decision maker to control the cellular response to pathogens and tumours by regulating the expression of inflammatory mediators such as cytokines, chemokines or interferons. In addition to various in vivo mouse models, kidney transplant patients under mTOR inhibitor therapy allowed the elucidation of important innate immune functions regulated by mTOR in humans. The role of the mTOR pathway in macrophages and dendritic cells enhances our understanding of the immune system and suggests new therapeutic avenues for the regulation of pro- versus anti-inflammatory mediators with potential relevance to cancer therapy, the design of novel adjuvants and the control of distinct infectious and autoimmune diseases.

scholarly journals Immunity and Tolerance Induced by Intestinal Mucosal Dendritic Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Julio Aliberti
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Food Allergies ◽  
Commensal Flora ◽  
Inflammatory Conditions ◽  
Mucosal Surfaces ◽  
Dendritic Cell Population ◽  
Proinflammatory Responses ◽  
Environmental Antigens

Dendritic cells present in the digestive tract are constantly exposed to environmental antigens, commensal flora, and invading pathogens. Under steady-state conditions, these cells have high tolerogenic potential, triggering differentiation of regulatory T cells to protect the host from unwanted proinflammatory immune responses to innocuous antigens or commensals. On the other hand, these cells must discriminate between commensal flora and invading pathogens and mount powerful immune response against pathogens. A potential result of unbalanced tolerogenic versus proinflammatory responses mediated by dendritic cells is associated with chronic inflammatory conditions, such as Crohn’s disease, ulcerative colitis, food allergies, and celiac disease. Herein, we review the dendritic cell population involved in mediating tolerance and immunity in mucosal surfaces, the progress in unveiling their development in vivo, and factors that can influence their functions.

A MATHEMATICAL MODEL TO ASSESS THE IMMUNE RESPONSE AGAINSTTRYPANOSOMA CRUZIINFECTION

2015 ◽  
Vol 23 (01) ◽  
pp. 131-163 ◽  
Author(s):  
HYUN MO YANG
Keyword(s):  
Mathematical Model ◽  
Trypanosoma Cruzi ◽  
Immune Responses ◽  
Cellular Response ◽  
Humoral Response ◽  
Cellular Responses ◽  
Cellular Immune Responses ◽  
Trivial Equilibrium ◽  
Cellular Immune ◽  
Cruzi Infection

A mathematical model is developed to assess humoral and cellular immune responses against Trypanosoma cruzi infection. Analysis of the model shows a unique non-trivial equilibrium, which is locally asymptotically stable, except in the case of a strong cellular response. When the proliferation of the activated CD8 T cells is increased, this equilibrium becomes unstable and a limit cycle appears. However, this behavior can be avoided by increasing the action of the humoral response. Therefore, unbalanced humoral and cellular responses can be responsible for long asymptomatic period, and the control of Trypanosoma cruzi infection is a consequence of well coordinated action of both humoral and cellular responses.

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