scholarly journals Dendritic Cells (DCs) as “Fire Accelerants” of Hantaviral Pathogenesis

Viruses ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 849 ◽  
Author(s):  
Günther Schönrich ◽  
Martin J. Raftery
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Immune Cells ◽  
Geographical Location ◽  
Hantavirus Pulmonary Syndrome ◽  
Haemorrhagic Fever ◽  
Prominent Feature ◽  
Cytopathic Effects ◽  
Human Immune ◽  
Excessive Activation

Hantaviruses are widespread zoonotic pathogens found around the globe. Depending on their geographical location, hantaviruses can cause two human syndromes, haemorrhagic fever with renal syndrome (HFRS) or hantavirus pulmonary syndrome (HPS). HPS and HFRS have many commonalities amongst which excessive activation of immune cells is a prominent feature. Hantaviruses replicate in endothelial cells (ECs), the major battlefield of hantavirus-induced pathogenesis, without causing cytopathic effects. This indicates that a misdirected response of human immune cells to hantaviruses is causing damage. As dendritic cells (DCs) orchestrate antiviral immune responses, they are in the focus of research analysing hantavirus-induced immunopathogenesis. In this review, we discuss the interplay between hantaviruses and DCs and the immunological consequences thereof.

scholarly journals The fate of influenza A virus after infection of human macrophages and dendritic cells

2012 ◽  
Vol 93 (11) ◽  
pp. 2315-2325 ◽  
Author(s):  
Kirsty R. Short ◽  
Andrew G. Brooks ◽  
Patrick C. Reading ◽  
Sarah L. Londrigan
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Influenza A Virus ◽  
Immune Cells ◽  
Influenza A ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Virus Release ◽  
Adaptive Immune ◽  
Human Immune

Airway macrophages (MΦ) and dendritic cells (DC) are important components of the innate host defence. Historically, these immune cells have been considered to play a critical role in controlling the severity of influenza A virus (IAV) infection by limiting virus release, initiating local inflammatory responses and by priming subsequent adaptive immune responses. However, some IAV strains have been reported to replicate productively in human immune cells. Potential amplification and dissemination of IAV from immune cells may therefore be an important virulence determinant. Herein, we will review findings in relation to the fate of IAV following infection of MΦ and DC. Insights regarding the consequences and outcomes of IAV infection of airway MΦ and DC are discussed in order to gain a better understanding of the pathogenesis of influenza virus.

scholarly journals Natural Killer Dendritic Cells Enhance Immune Responses Elicited byα-Galactosylceramide-Stimulated Natural Killer T Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Sung Won Lee ◽  
Hyun Jung Park ◽  
Nayoung Kim ◽  
Seokmann Hong
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Natural Killer ◽  
Immune Cells ◽  
Tumor Antigens ◽  
Nkt Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Natural Killer T

Natural killer dendritic cells (NKDCs) possess potent anti-tumor activity, but the cellular effect of NKDC interactions with other innate immune cells is unclear. In this study, we demonstrate that the interaction of NKDCs and natural killer T (NKT) cells is required for the anti-tumor immune responses that are elicited byα-galactosylceramide (α-GC) in mice. The rapid and strong expression of interferon-γby NKDCs afterα-GC stimulation was dependent on NKT cells. Various NK and DC molecular markers and cytotoxic molecules were up-regulated followingα-GC administration. This up-regulation could improve NKDC presentation of tumor antigens and increase cytotoxicity against tumor cells. NKDCs were required for the stimulation of DCs, NK cells, and NKT cells. The strong anti-tumor immune responses elicited byα-GC may be due to the down-regulation of regulatory T cells. Furthermore, the depletion of NKDCs dampened the tumor clearance mediated byα-GC-stimulated NKT cellsin vivo. Taken together, these results indicate that complex interactions of innate immune cells might be required to achieve optimal anti-tumor immune responses during the early stages of tumorigenesis.

scholarly journals Guanine-Modified Inhibitory Oligonucleotides Efficiently Impair TLR7- and TLR9-Mediated Immune Responses of Human Immune Cells

PLoS ONE ◽  
2015 ◽  
Vol 10 (2) ◽  
pp. e0116703 ◽  
Author(s):  
Franziska Römmler ◽  
Monika Hammel ◽  
Anna Waldhuber ◽  
Tina Müller ◽  
Marion Jurk ◽  
...  
Keyword(s):  
Immune Responses ◽  
Immune Cells ◽  
Human Immune

scholarly journals Lactate-Dependent Regulation of Immune Responses by Dendritic Cells and Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Indumathi Manoharan ◽  
Puttur D. Prasad ◽  
Muthusamy Thangaraju ◽  
Santhakumar Manicassamy
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Immune Cells ◽  
Adaptive Immune Responses ◽  
Effector Functions ◽  
Tissue Microenvironment ◽  
Adaptive Immune ◽  
Pathological Conditions ◽  
Recent Advances ◽  
Adaptive Immune Cells

For decades, lactate has been considered an innocuous bystander metabolite of cellular metabolism. However, emerging studies show that lactate acts as a complex immunomodulatory molecule that controls innate and adaptive immune cells’ effector functions. Thus, recent advances point to lactate as an essential and novel signaling molecule that shapes innate and adaptive immune responses in the intestine and systemic sites. Here, we review these recent advances in the context of the pleiotropic effects of lactate in regulating diverse functions of immune cells in the tissue microenvironment and under pathological conditions.

scholarly journals A comprehensive logic-based model of the human immune system to study the dynamics responses to mono- and coinfections

2020 ◽  
Author(s):  
Bhanwar Lal Puniya ◽  
Robert Moore ◽  
Akram Mohammed ◽  
Rada Amin ◽  
Alyssa La Fleur ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Immune Responses ◽  
Immune Cells ◽  
Computational Models ◽  
Single Infection ◽  
Human Immune System ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Human Immune

AbstractThe human immune system, which protects against pathogens and diseases, is a complex network of cells and molecules. The effects of complex dynamical interactions of pathogens and immune cells on the immune response can be studied using computational models. However, a model of the entire immune system is still lacking. Here, we developed a comprehensive computational model that integrates innate and adaptive immune cells, cytokines, immunoglobulins, and nine common pathogens from different classes of virus, bacteria, parasites, and fungi. This model was used to investigate the dynamics of the immune system under two scenarios: (1) single infection with pathogens, and (2) various medically relevant pathogen coinfections. In coinfections, we found that the order of infecting pathogens has a significant impact on the dynamics of cytokines and immunoglobulins. Thus, our model provides a tool to simulate immune responses under different dosage of pathogens and their combinations, which can be further extended and used as a tool for drug discovery and immunotherapy. Furthermore, the model provides a comprehensive and simulatable blueprint of the human immune system as a result of the synthesis of the vast knowledge about the network-like interactions of various components of the system.

scholarly journals Helminth Excreted/Secreted Antigens Repress Expression of LPS-Induced Let-7i but Not miR-146a and miR-155 in Human Dendritic Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Luis I. Terrazas ◽  
Fausto Sánchez-Muñoz ◽  
Magaly Pérez-Miranda ◽  
Ana M. Mejía-Domínguez ◽  
Yadira Ledesma-Soto ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Inflammatory Response ◽  
Immune Responses ◽  
Immune Cells ◽  
Helminth Parasites ◽  
Taenia Crassiceps ◽  
Mirnas Expression ◽  
Human Dendritic Cells ◽  
Secreted Antigens

MicroRNAs have emerged as key regulators of immune responses. They influence immune cells' function and probably the outcome of several infections. Currently, it is largely unknown if helminth parasites and their antigens modify host microRNAs expression. The aim of this study was to explore if excreted/secreted antigens ofTaenia crassicepsregulate LPS-induced miRNAs expression in human Dendritic Cells. We found that these antigens repressed LPS-let-7i induction but not mir-146a or mir-155 and this correlates with a diminished inflammatory response. This let-7i downregulation in Dendritic Cells constitutes a novel feature of the modulatory activity that helminth-derived antigens exert on their host.

scholarly journals Dendritic Cells The Tumor Microenvironment and the Challenges for an Effective Antitumor Vaccination

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Fabian Benencia ◽  
Leslee Sprague ◽  
John McGinty ◽  
Michelle Pate ◽  
Maria Muccioli
Keyword(s):  
Clinical Trials ◽  
Dendritic Cells ◽  
Tumor Microenvironment ◽  
Immune Responses ◽  
Immune Cells ◽  
Therapeutic Potential ◽  
Human Cancer ◽  
Dc Vaccines ◽  
Tumor Clearance ◽  
Antigen Presenting

Many clinical trials have been carried out or are in progress to assess the therapeutic potential of dendritic-cell- (DC-) based vaccines on cancer patients, and recently the first DC-based vaccine for human cancer was approved by the FDA. Herewith, we describe the general characteristics of DCs and different strategies to generate effective antitumor DC vaccines. In recent years, the relevance of the tumor microenvironment in the progression of cancer has been highlighted. It has been shown that the tumor microenvironment is capable of inactivating various components of the immune system responsible for tumor clearance. In particular, the effect of the tumor microenvironment on antigen-presenting cells, such as DCs, does not only render these immune cells unable to induce specific immune responses, but also turns them into promoters of tumor growth. We also describe strategies likely to increase the efficacy of DC vaccines by reprogramming the immunosuppressive nature of the tumor microenvironment.

Monocytes and dendritic cells are the primary sources of interleukin 37 in human immune cells

2016 ◽  
Vol 101 (4) ◽  
pp. 901-911 ◽  
Author(s):  
Ina Rudloff ◽  
Steven X. Cho ◽  
Jason C. Lao ◽  
Devi Ngo ◽  
Matthew McKenzie ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Cells ◽  
Primary Sources ◽  
Human Immune

Should we Try to Alleviate Immunosenescence and Inflammaging - Why, How and to What Extent?

2019 ◽  
Vol 25 (39) ◽  
pp. 4154-4162 ◽  
Author(s):  
Jacek M. Witkowski ◽  
Ewa Bryl ◽  
Tamas Fulop
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Immune Cells ◽  
Malignant Neoplasm ◽  
Human Beings ◽  
Therapeutic Approaches ◽  
Human Immune System ◽  
Immune Systems ◽  
Human Immune

With advancing age, immune responses of human beings to external pathogens, i.e., bacteria, viruses, fungi and parasites, and to internal pathogens - malignant neoplasm cells - become less effective. Two major features in the process of aging of the human immune system are immunosenescence and inflammaging. The immune systems of our predecessors co-evolved with pathogens, which led to the occurrence of effective immunity. However, the otherwise beneficial activity may pose problems to the organism of the host and so it has builtin brakes (regulatory immune cells) and - with age - it undergoes adaptations and modifications, examples of which are the mentioned inflammaging and immunosenescence. Here we describe the mechanisms that first created our immune systems, then the consequences of their changes associated with aging, and the mechanisms of inflammaging and immunosenescence. Finally, we discuss to what extent both processes are detrimental and to what extent they might be beneficial and propose some therapeutic approaches for their wise control.

scholarly journals Nef Dimerization Defect Abrogates HIV Viremia and Associated Immune Dysregulation in the Bone Marrow-Liver-Thymus-Spleen (BLTS) Humanized Mouse Model.

2021 ◽  
Author(s):  
Shivkumar Biradar ◽  
Yash Agarwal ◽  
Antu Das ◽  
Sherry T. Shu ◽  
Jasmine Samal ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Antiretroviral Therapy ◽  
Mouse Model ◽  
Immune Responses ◽  
Immune Cells ◽  
Therapeutic Target ◽  
Immune Dysregulation ◽  
Humanized Mouse ◽  
Humanized Mouse Model ◽  
Human Immune

Abstract BackgroundLoss of function mutations in the human immunodeficiency virus (HIV) negative factor (nef) gene are associated with reduced viremia, robust T cell immune responses, and delayed acquired immunodeficiency syndrome (AIDS) progression in humans. Importantly, Nef persists in antiretroviral therapy-treated chronic HIV-infected individuals. In vitro studies have shown that mutations in the Nef dimerization interface significantly attenuate viral replication and impair host defense. However, in vivo, mechanistic studies on the role of Nef dimerization in HIV infection are lacking. Humanized rodents with human immune cells are robust platforms for investigating the interactions between HIV and the human immune system. The bone marrow-liver-thymus-spleen (BLTS) humanized mouse model carries human immune cells and lymphoid tissues that facilitate anti-viral immune responses. ResultsHere, we demonstrate that nef deletion abrogates HIV viremia and HIV-induced immune dysregulation in the BLTS-humanized mouse model. Furthermore, we demonstrate that preventing Nef dimerization abrogates HIV viremia and HIV-induced immune dysregulation in the BLTS-humanized mouse model. We also demonstrate that viremic control of HIV carrying deletion or dimerization defects in nef is associated with robust antiviral innate immune signaling, T helper 1 (Th1) signaling, and reduced expression of Programmed cell death protein 1 (PD1) on T cells.ConclusionsOur results suggest that Nef dimerization may be a therapeutic target for adjuvants in immune-mediated HIV cure strategies. Furthermore, Nef dimerization may be a therapeutic target for ameliorating the residual immune dysregulation in antiretroviral therapy-treated chronic HIV-infected individuals.

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