scholarly journals Dendritic Cells and SARS-CoV-2 Infection: Still an Unclarified Connection

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2046
Author(s):  
Pasquale Campana ◽  
Valentina Parisi ◽  
Dario Leosco ◽  
Debora Bencivenga ◽  
Fulvio Della Ragione ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Viral Infections ◽  
Immunological Response ◽  
Organ Damage ◽  
Molecular Response ◽  
Adaptive Immune ◽  
Molecular Events ◽  
Humanized Monoclonal Antibodies ◽  
Major Emphasis ◽  
Initial Process

The ongoing pandemic due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has so far infected about 2.42 × 107 (as at 27 August 2020) subjects with more than 820,000 deaths. It is the third zoonotic coronavirus-dependent outbreak in the last twenty years and represents a major infective threat for public health worldwide. A main aspect of the infection, in analogy to other viral infections, is the so-called “cytokine storm”, an inappropriate molecular response to virus spread which plays major roles in tissue and organ damage. Immunological therapies, including vaccines and humanized monoclonal antibodies, have been proposed as major strategies for prevention and treatment of the disease. Accordingly, a detailed mechanistic knowledge of the molecular events with which the virus infects cells and induces an immunological response appears necessary. In this review, we will report details of the initial process of SARS-CoV-2 cellular entry with major emphasis on the maturation of the spike protein. Then, a particular focus will be devoted to describe the possible mechanisms by which dendritic cells, a major cellular component of innate and adaptive immune responses, may play a role in the spread of the virus in the human body and in the clinical evolution of the disease.

scholarly journals Dendritic cells and isolevuglandins in immunity, inflammation, and hypertension

2017 ◽  
Vol 312 (3) ◽  
pp. H368-H374 ◽  
Author(s):  
Kala B. Dixon ◽  
Sean S. Davies ◽  
Annet Kirabo
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Protein Modification ◽  
Vascular Dysfunction ◽  
Organ Damage ◽  
Activated T Cells ◽  
Adaptive Immune ◽  
The Past ◽  
Antigen Presenting

Hypertension is the major risk factor for morbidity and mortality from myocardial infarction, stroke, heart failure, and chronic kidney disease. Despite its importance, the pathogenesis of essential hypertension is poorly understood. During the past several years, it has become evident that T cells contribute to hypertension. Activated T cells accumulate in the perivascular space and the kidney and release cytokines that promote vascular dysfunction and end-organ damage. Although dendritic cells play a pivotal role in initiating adaptive immune responses, T cells have taken center stage in studies implicating the immune system in the genesis of hypertension. The mechanisms by which T cells are activated and the antigens involved are poorly understood. We recently showed that hypertension is associated with increased dendritic cell production of the TH17 polarizing cytokines, IL-6, IL-1β, and IL-23. This occurs in part by increased superoxide production via NADPH oxidase and protein modification by highly reactive isolevuglandins (IsoLGs). IsoLGs are produced via the isoprostane pathway of free radical-mediated lipid peroxidation and, when adducted to proteins, have the potential to act as neoantigens. In this review, we discuss recent advances in our understanding of the role of antigen-presenting dendritic cells in the pathophysiology of hypertension and highlight potential neoantigens that may contribute to this disease.

scholarly journals Adaptive Immune Responses in Primary Cutaneous Sarcoidosis

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Matteo Bordignon ◽  
Paola Rottoli ◽  
Carlo Agostini ◽  
Mauro Alaibac
Keyword(s):  
Dendritic Cells ◽  
Treatment Strategies ◽  
Immunological Response ◽  
Inflammatory Disorder ◽  
Cutaneous Sarcoidosis ◽  
Cutaneous Lesions ◽  
Adaptive Immune ◽  
Immunological Mechanisms ◽  
Adaptive Immune Systems

Sarcoidosis is a multisystemic inflammatory disorder with cutaneous lesions present in about one-quarter of the patients. Cutaneous lesions have been classified as specific and nonspecific, depending on the presence of nonnecrotizing epithelial cell granulomas on histologic studies. The development and progression of specific cutaneous sarcoidosis involves a complex interaction between cells of the adaptive immune systems, notably T-lymphocytes and dendritic cells. In this paper, we will discuss the role of T-cells and skin dendritic cells in the development of primary cutaneous sarcoidosis and comment on the potential antigenic stimuli that may account for the development of the immunological response. We will further explore the contributions of selected cytokines to the immunopathological process. The knowledge of the adaptive immunological mechanisms operative in cutaneous sarcoidosis may subsequently be useful for identifying prevention and treatment strategies of systemic sarcoidosis.

scholarly journals The Inability of Wild-Type Rabies Virus To Activate Dendritic Cells Is Dependent on the Glycoprotein and Correlates with Its Low Level of theDe Novo-Synthesized Leader RNA

2014 ◽  
Vol 89 (4) ◽  
pp. 2157-2169 ◽  
Author(s):  
Yang Yang ◽  
Ying Huang ◽  
Clement W. Gnanadurai ◽  
Shengbo Cao ◽  
Xueqin Liu ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Rabies Virus ◽  
Adoptive Transfer ◽  
Viral Infections ◽  
De Novo ◽  
Wild Type ◽  
Adaptive Immune Responses ◽  
Low Level ◽  
Adaptive Immune

ABSTRACTDendritic cells (DCs) are the most efficient antigen-presenting cells, playing a key role in the adaptive immune responses to viral infections. Our studies demonstrate that wild-type (wt) rabies virus (RABV) does not activate DCs. Adoptive transfer of DCs primed with wt RABV did not activate DCs, stimulate virus neutralizing antibodies (VNA), or protect recipients against challenge. However, adoptive transfer of DCs primed with laboratory-attenuated RABV resulted in DC activation, production of VNA, and protection against challenge.In vitrostudies with recombinant RABV (laboratory-attenuated RABV expressing the glycoprotein or the phosphoprotein from wt RABV) demonstrate that DC activation is dependent on the glycoprotein and involves the IPS-1 pathway. Furthermore, binding to and entry into DCs by wt RABV is severely blocked, and the copy number ofde novo-synthesized leader RNA was two logs lower in DCs infected with the wt than in DCs treated with laboratory-attenuated RABV. However, transient transfection of DCs with synthesized leader RNA from either wt or attenuated RABV is capable of activating DCs in a dose-dependent manner. Thus, the inability of wt RABV to activate DCs correlates with its low level of thede novo-synthesized leader RNA.IMPORTANCERabies remains a public health threat, with more than 55,000 fatalities each year around the world. Since DCs play a key role in the adaptive immune responses to viral infections, we investigated the ability of rabies virus (RABV) to activate DCs. It was found that the adoptive transfer of DCs primed with wt RABV did not activate DCs, stimulate VNA, or protect mice against lethal challenge. However, laboratory-attenuated RABV mediates the activation of DCs via the IPS-1 pathway and is glycoprotein dependent. We further show that wt RABV evades DC-mediated immune activation by inefficient binding/entry into DCs and as a result of a reduced level ofde novo-synthesized leader RNA. These findings may have important implications in the development of efficient rabies vaccines.

scholarly journals The Contact Allergen NiSO4 Triggers a Distinct Molecular Response in Primary Human Dendritic Cells Compared to Bacterial LPS

2021 ◽  
Vol 12 ◽  
Author(s):  
Tessa Höper ◽  
Katherina Siewert ◽  
Verónica I. Dumit ◽  
Martin von Bergen ◽  
Kristin Schubert ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Binding Capacity ◽  
Contact Allergy ◽  
Cholesterol Biosynthesis ◽  
Immunological Response ◽  
Human Monocyte ◽  
Cholesterol Depletion ◽  
Related Factor ◽  
Molecular Response ◽  
Activation Markers

Dendritic cells (DC) play a central role in the pathogenesis of allergic contact dermatitis (ACD), the most prevalent form of immunotoxicity in humans. However, knowledge on allergy-induced DC maturation is still limited and proteomic studies, allowing to unravel molecular effects of allergens, remain scarce. Therefore, we conducted a global proteomic analysis of human monocyte-derived dendritic cells (MoDC) treated with NiSO4, the most prominent cause of ACD and compared proteomic alterations induced by NiSO4 to the bacterial trigger lipopolysaccharide (LPS). Both substances possess a similar toll-like receptor (TLR) 4 binding capacity, allowing to identify allergy-specific effects compared to bacterial activation. MoDCs treated for 24 h with 2.5 μg/ml LPS displayed a robust immunological response, characterized by upregulation of DC activation markers, secretion of pro-inflammatory cytokines and stimulation of T cell proliferation. Similar immunological reactions were observed after treatment with 400 μM NiSO4 but less pronounced. Both substances triggered TLR4 and triggering receptor expressed on myeloid cells (TREM) 1 signaling. However, NiSO4 also activated hypoxic and apoptotic pathways, which might have overshadowed initial signaling. Moreover, our proteomic data support the importance of nuclear factor erythroid 2-related factor 2 (Nrf2) as a key player in sensitization since many Nrf2 targets genes were strongly upregulated on protein and gene level selectively after treatment with NiSO4. Strikingly, NiSO4 stimulation induced cellular cholesterol depletion which was counteracted by the induction of genes and proteins relevant for cholesterol biosynthesis. Our proteomic study allowed for the first time to better characterize some of the fundamental differences between NiSO4 and LPS-triggered activation of MoDCs, providing an essential contribution to the molecular understanding of contact allergy.

Combining PD-L1 Inhibitors with Immunogenic Cell Death Triggered by Chemo-Photothermal therapy via a Thermosensitive Liposome System to Stimulate Tumor-specific Immunological Response

Nanoscale ◽  
2021 ◽  
Author(s):  
Jie Yu ◽  
Xidong He ◽  
Zigui Wang ◽  
Yu Peng Wang ◽  
Sha Liu ◽  
...  
Keyword(s):  
Cell Death ◽  
Immune Responses ◽  
Photothermal Therapy ◽  
Immunological Response ◽  
Immune Checkpoint Blockade ◽  
Immunogenic Cell Death ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Thermosensitive Liposome ◽  
Liposome System

Immune checkpoint blockade (ICB) therapy in combination with immunogenic death (ICD) triggered by photothermal therapy (PTT) and oxaliplatin (OXA) treatment was expected to elicit both innate and adaptive immune responses...

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 MRGPR-mediated activation of local mast cells clears cutaneous bacterial infection and protects against reinfection

2019 ◽  
Vol 5 (1) ◽  
pp. eaav0216 ◽  
Author(s):  
Mohammad Arifuzzaman ◽  
Yuvon R. Mobley ◽  
Hae Woong Choi ◽  
Pradeep Bist ◽  
Cristina A. Salinas ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Wound Healing ◽  
Dendritic Cells ◽  
Mast Cells ◽  
Connective Tissue ◽  
Selective Activation ◽  
Adaptive Immune ◽  
Antigen Presenting ◽  
G Protein Coupled ◽  
Draining Lymph Nodes

Mast cells (MCs) are strategically distributed at barrier sites and prestore various immunocyte-recruiting cytokines, making them ideal targets for selective activation to treat peripheral infections. Here, we report that topical treatment with mastoparan, a peptide MC activator (MCA), enhances clearance ofStaphylococcus aureusfrom infected mouse skins and accelerates healing of dermonecrotic lesions. Mastoparan functions by activating connective tissue MCs (CTMCs) via the MRGPRX2 (Mas-related G protein-coupled receptor member X2) receptor. Peripheral CTMC activation, in turn, enhances recruitment of bacteria-clearing neutrophils and wound-healing CD301b+dendritic cells. Consistent with MCs playing a master coordinating role, MC activation also augmented migration of various antigen-presenting dendritic cells to draining lymph nodes, leading to stronger protection against a second infection challenge. MCAs therefore orchestrate both the innate and adaptive immune arms, which could potentially be applied to combat peripheral infections by a broad range of pathogens.

scholarly journals Viral Infections and Autoimmune Disease: Roles of LCMV in Delineating Mechanisms of Immune Tolerance

Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 885
Author(s):  
Georgia Fousteri ◽  
Amy Dave Jhatakia
Keyword(s):  
Immune System ◽  
Autoimmune Disease ◽  
Viral Infections ◽  
Molecular Mimicry ◽  
Short Review ◽  
Organ Damage ◽  
Lymphocytic Choriomeningitis ◽  
Immune Deviation ◽  
Viral Pathogen ◽  
Lcmv Infection

Viral infections are a natural part of our existence. They can affect us in many ways that are the result of the interaction between the viral pathogen and our immune system. Most times, the resulting immune response is beneficial for the host. The pathogen is cleared, thus protecting our vital organs with no other consequences. Conversely, the reaction of our immune system against the pathogen can cause organ damage (immunopathology) or lead to autoimmune disease. To date, there are several mechanisms for virus-induced autoimmune disease, including molecular mimicry and bystander activation, in support of the “fertile field” hypothesis (terms defined in our review). In contrast, viral infections have been associated with protection from autoimmunity through mechanisms that include Treg invigoration and immune deviation, in support of the “hygiene hypothesis”, also defined here. Infection with lymphocytic choriomeningitis virus (LCMV) is one of the prototypes showing that the interaction of our immune system with viruses can either accelerate or prevent autoimmunity. Studies using mouse models of LCMV have helped conceive and establish several concepts that we now know and use to explain how viruses can lead to autoimmune activation or induce tolerance. Some of the most important mechanisms established during the course of LCMV infection are described in this short review.

scholarly journals Lentiviral Transduction of Dendritic Cells Confers Protective Antiviral Immunity In Vivo

2004 ◽  
Vol 78 (14) ◽  
pp. 7843-7845 ◽  
Author(s):  
Shohreh Zarei ◽  
Shahnaz Abraham ◽  
Jean-Francois Arrighi ◽  
Olivier Haller ◽  
Thomas Calzascia ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Viral Infections ◽  
Cytotoxic T Lymphocyte ◽  
Antiviral Immunity ◽  
Lymphocytic Choriomeningitis ◽  
Lymphocyte Response ◽  
Vaccine Candidates ◽  
Virus Model ◽  
Cytotoxic T Lymphocyte Response

ABSTRACT Control of a viral infection in vivo requires a rapid and efficient cytotoxic-T-lymphocyte response. We demonstrate that lentivirus-mediated introduction of antigen in dendritic cells confers a protective antiviral immunity in vivo in a lymphocytic choriomeningitis virus model. Therefore, lentiviral vectors may be excellent vaccine candidates for viral infections.

scholarly journals Effects of Staphylococcus aureus Bacteriophage K on Expression of Cytokines and Activation Markers by Human Dendritic Cells In Vitro

Viruses ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 617 ◽  
Author(s):  
Helen Freyberger ◽  
Yunxiu He ◽  
Amanda Roth ◽  
Mikeljon Nikolich ◽  
Andrey Filippov
Keyword(s):  
Staphylococcus Aureus ◽  
Dendritic Cells ◽  
Inflammatory Response ◽  
Adaptive Immune Response ◽  
Human Monocyte ◽  
Activation Markers ◽  
Mhc I ◽  
Adaptive Immune ◽  
Human Dendritic Cells

A potential concern with bacteriophage (phage) therapeutics is a host-versus-phage response in which the immune system may neutralize or destroy phage particles and thus impair therapeutic efficacy, or a strong inflammatory response to repeated phage exposure might endanger the patient. Current literature is discrepant with regard to the nature and magnitude of innate and adaptive immune response to phages. The purpose of this work was to study the potential effects of Staphylococcus aureus phage K on the activation of human monocyte-derived dendritic cells. Since phage K acquired from ATCC was isolated around 90 years ago, we first tested its activity against a panel of 36 diverse S. aureus clinical isolates from military patients and found that it was lytic against 30/36 (83%) of strains. Human monocyte-derived dendritic cells were used to test for an in vitro phage-specific inflammatory response. Repeated experiments demonstrated that phage K had little impact on the expression of pro- and anti-inflammatory cytokines, or on MHC-I/II and CD80/CD86 protein expression. Given that dendritic cells are potent antigen-presenting cells and messengers between the innate and the adaptive immune systems, our results suggest that phage K does not independently affect cellular immunity or has a very limited impact on it.

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