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 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 Rapamycin Alternatively Modifies Mitochondrial Dynamics in Dendritic Cells to Reduce Kidney Ischemic Reperfusion Injury

2021 ◽  
Vol 22 (10) ◽  
pp. 5386
Author(s):  
Maria Namwanje ◽  
Bijay Bisunke ◽  
Thomas V. Rousselle ◽  
Gene G. Lamanilao ◽  
Venkatadri S. Sunder ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Mitochondrial Dynamics ◽  
Graft Loss ◽  
Kidney Injury ◽  
Adaptive Immune ◽  
Consumption Rates ◽  
Regulatory Phenotype

Dendritic cells (DCs) are unique immune cells that can link innate and adaptive immune responses and Immunometabolism greatly impacts their phenotype. Rapamycin is a macrolide compound that has immunosuppressant functions and is used to prevent graft loss in kidney transplantation. The current study evaluated the therapeutic potential of ex-vivo rapamycin treated DCs to protect kidneys in a mouse model of acute kidney injury (AKI). For the rapamycin single (S) treatment (Rapa-S-DC), Veh-DCs were treated with rapamycin (10 ng/mL) for 1 h before LPS. In contrast, rapamycin multiple (M) treatment (Rapa-M-DC) were exposed to 3 treatments over 7 days. Only multiple ex-vivo rapamycin treatments of DCs induced a persistent reprogramming of mitochondrial metabolism. These DCs had 18-fold more mitochondria, had almost 4-fold higher oxygen consumption rates, and produced more ATP compared to Veh-DCs (Veh treated control DCs). Pathway analysis showed IL10 signaling as a major contributing pathway to the altered immunophenotype after Rapamycin treatment compared to vehicle with significantly lower cytokines Tnfa, Il1b, and Il6, while regulators of mitochondrial content Pgc1a, Tfam, and Ho1 remained elevated. Critically, adoptive transfer of rapamycin-treated DCs to WT recipients 24 h before bilateral kidney ischemia significantly protected the kidneys from injury with a significant 3-fold improvement in kidney function. Last, the infusion of DCs containing higher mitochondria numbers (treated ex-vivo with healthy isolated mitochondria (10 µg/mL) one day before) also partially protected the kidneys from IRI. These studies demonstrate that pre-emptive infusion of ex-vivo reprogrammed DCs that have higher mitochondria content has therapeutic capacity to induce an anti-inflammatory regulatory phenotype to protect kidneys from injury.

scholarly journals CD8+lineage dendritic cells determine adaptive immune responses to inflammasome activation upon sterile skin injury

2017 ◽  
Vol 27 (1) ◽  
pp. 71-79 ◽  
Author(s):  
Rituparna Chakraborty ◽  
Janin Chandra ◽  
Shuai Cui ◽  
Lynn Tolley ◽  
Matthew A. Cooper ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Inflammasome Activation ◽  
Adaptive Immune Responses ◽  
Skin Injury ◽  
Adaptive Immune

scholarly journals Dendritic Cells in Innate and Adaptive Immune Responses against Influenza Virus

Viruses ◽  
2009 ◽  
Vol 1 (3) ◽  
pp. 1022-1034 ◽  
Author(s):  
Artur Summerfield ◽  
Kenneth McCullough
Keyword(s):  
Dendritic Cells ◽  
Influenza Virus ◽  
Immune Responses ◽  
Adaptive Immune Responses ◽  
Adaptive Immune

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 The Differential Anti-HIV Effect of a New Humic Substance-Derived Preparation in Diverse Cells of the Immune System

Acta Naturae ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 68-76
Author(s):  
G. V. Kornilaeva ◽  
A. E. Siniavin ◽  
A. Schultz ◽  
A. Germann ◽  
C. Moog ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Lymphocytes ◽  
Humic Substance ◽  
Immune Cells ◽  
Cell Types ◽  
Inhibitory Effect ◽  
Infection Inhibition ◽  
Toxic Concentrations ◽  
Anti Hiv ◽  
Hiv 1

The anti-HIV activity of a new humic substance-derived preparation has been studied in individual pools of immune cells (CD4+ T lymphocytes, macrophages, dendritic cells). Near-complete inhibition of the HIV infection (by more than 90%) was achieved by treating each of the abovementioned cell types with non-toxic concentrations of the preparation. The inhibitory effect demonstrates the possibility of preventing the depletion of a significant portion of functionally important immune cells. A comparative study of infection inhibition in individual cell pools has allowed us to reveal the differences in the preparations effectiveness in each of the cell populations. A R5-tropic HIV-1 infection in macrophages exhibited maximum sensitivity to the preparation: 90% and 50% inhibition of the infection were observed in the presence of concentrations as low as 1.4 and 0.35 g/ml, respectively. A 15- and 19-fold higher concentration was required to achieve the same extent of inhibition in dendritic cells infected with the same strain. The effectiveness of the drug in CD4 + T lymphocytes is quite comparable to its effectiveness in macrophages. The drug is universally effective for both the T- and M-tropic variants of HIV-1.

scholarly journals Immunogenicity, safety, and efficacy of sequential immunizations with an SIV-based IDLV expressing CH505 Envs

npj Vaccines ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Maria Blasi ◽  
Donatella Negri ◽  
Kevin O. Saunders ◽  
Erich J. Baker ◽  
Hannah Stadtler ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Lentiviral Vector ◽  
Rhesus Macaques ◽  
Infected Individual ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Safety And Efficacy ◽  
Env Protein ◽  
Hiv 1

AbstractA preventative HIV-1 vaccine is an essential intervention needed to halt the HIV-1 pandemic. Neutralizing antibodies protect against HIV-1 infection in animal models, and thus an approach toward a protective HIV-1 vaccine is to induce broadly cross-reactive neutralizing antibodies (bnAbs). One strategy to achieve this goal is to define envelope (Env) evolution that drives bnAb development in infection and to recreate those events by vaccination. In this study, we report the immunogenicity, safety, and efficacy in rhesus macaques of an SIV-based integrase defective lentiviral vector (IDLV) expressing sequential gp140 Env immunogens derived from the CH505 HIV-1-infected individual who made the CH103 and CH235 bnAb lineages. Immunization with IDLV expressing sequential CH505 Envs induced higher magnitude and more durable binding and neutralizing antibody responses compared to protein or DNA +/− protein immunizations using the same sequential envelopes. Compared to monkeys immunized with a vector expressing Envs alone, those immunized with the combination of IDLV expressing Env and CH505 Env protein demonstrated improved durability of antibody responses at six months after the last immunization as well as lower peak viremia and better virus control following autologous SHIV-CH505 challenge. There was no evidence of vector mobilization or recombination in the immunized and challenged monkeys. Although the tested vaccines failed to induce bnAbs and to mediate significant protection following SHIV-challenge, our results show that IDLV proved safe and successful at inducing higher titer and more durable immune responses compared to other vaccine platforms.

scholarly journals Dendritic Cells/Macrophages-Targeting Feature of Ebola Glycoprotein and its Potential as Immunological Facilitator for Antiviral Vaccine Approach

2019 ◽  
Vol 7 (10) ◽  
pp. 402
Author(s):  
Titus Abiola Olukitibi ◽  
Zhujun Ao ◽  
Mona Mahmoudi ◽  
Gary A. Kobinger ◽  
Xiaojian Yao
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Ebola Virus ◽  
Vaccine Development ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Immunological Approach ◽  
Vaccine Approach ◽  
Acquired Immune Responses ◽  
Diverse Virus

In the prevention of epidemic and pandemic viral infection, the use of the antiviral vaccine has been the most successful biotechnological and biomedical approach. In recent times, vaccine development studies have focused on recruiting and targeting immunogens to dendritic cells (DCs) and macrophages to induce innate and adaptive immune responses. Interestingly, Ebola virus (EBOV) glycoprotein (GP) has a strong binding affinity with DCs and macrophages. Shreds of evidence have also shown that the interaction between EBOV GP with DCs and macrophages leads to massive recruitment of DCs and macrophages capable of regulating innate and adaptive immune responses. Therefore, studies for the development of vaccine can utilize the affinity between EBOV GP and DCs/macrophages as a novel immunological approach to induce both innate and acquired immune responses. In this review, we will discuss the unique features of EBOV GP to target the DC, and its potential to elicit strong immune responses while targeting DCs/macrophages. This review hopes to suggest and stimulate thoughts of developing a stronger and effective DC-targeting vaccine for diverse virus infection using EBOV GP.

scholarly journals Impact of HMGB1/TLR Ligand Complexes on HIV-1 Replication: Possible Role for Flagellin during HIV-1 Infection

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Piotr Nowak ◽  
Samir Abdurahman ◽  
Annica Lindkvist ◽  
Marius Troseid ◽  
Anders Sönnerborg
Keyword(s):  
Immune Responses ◽  
Cpg Odn ◽  
Cell Necrosis ◽  
Adaptive Immune ◽  
Microbial Product ◽  
P24 Antigen ◽  
Culture Supernatants ◽  
Hiv 1

Objective. We hypothesized that HMGB1 in complex with bacterial components, such as flagellin, CpG-ODN, and LPS, promotes HIV-1 replication. Furthermore, we studied the levels of antiflagellin antibodies during HIV-1-infection.Methods. Chronically HIV-1-infected U1 cells were stimulated with necrotic extract/recombinant HMGB1 in complex with TLR ligands or alone. HIV-1 replication was estimated by p24 antigen in culture supernatants 48–72 hours after stimulation. The presence of systemic anti-flagellin IgG was determined in 51 HIV-1-infected patients and 19 controls by immunoblotting or in-house ELISA.Results. Flagellin, LPS, and CpG-ODN induced stronger HIV-1 replication when incubated together with necrotic extract or recombinant HMGB1 than activation by any of the compounds alone. Moreover, the stimulatory effect of necrotic extract was inhibited by depletion of HMGB1. Elevated levels of anti-flagellin antibodies were present in plasma from HIV-1-infected patients and significantly decreased during 2 years of antiretroviral therapy.Conclusions. Our findings implicate a possible role of HGMB1-bacterial complexes, as a consequence of microbial translocation and cell necrosis, for immune activation in HIV-1 pathogenesis. We propose that flagellin is an important microbial product, that modulates viral replication and induces adaptive immune responsesin vivo.

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