scholarly journals Physiological Role of Plasmacytoid Dendritic Cells and Their Potential Use in Cancer Immunity

2008 ◽  
Vol 2008 ◽  
pp. 1-10 ◽  
Author(s):  
Jorge Schettini ◽  
Pinku Mukherjee
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Tumor Antigens ◽  
Physiological Role ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
Therapeutic Approaches ◽  
Adaptive Immune ◽  
Type I Ifns

Dendritic cells (DCs) play a pivotal role in the control of innate and adaptive immune responses. They are a heterogeneous cell population, where plasmacytoid dendritic cells (pDCs) are a unique subset capable of secreting high levels of type I IFNs. It has been demonstrated that pDCs can coordinate events during the course of viral infection, atopy, autoimmune diseases, and cancer. Therefore, pDC, as a main source of type I IFN, is an attractive target for therapeutic manipulations of the immune system to elicit a powerful immune response against tumor antigens in combination with other therapies. The therapeutic vaccination with antigen-pulsed DCs has shown a limited efficacy to generate an effective long-lasting immune response against tumor cells. A rational manipulation and design of vaccines which could include DC subsets outside “Langerhans cell paradigm” might allow us to improve the therapeutic approaches for cancer patients.

scholarly journals A pathogenic role of plasmacytoid dendritic cells in autoimmunity and chronic viral infection

2019 ◽  
Vol 216 (9) ◽  
pp. 1974-1985 ◽  
Author(s):  
Franck J. Barrat ◽  
Lishan Su
Keyword(s):  
Dendritic Cells ◽  
Viral Infections ◽  
Plasmacytoid Dendritic Cells ◽  
Chronic Viral Infection ◽  
Type I ◽  
Main Function ◽  
Pathogenic Role ◽  
Type I Ifns ◽  
Chronic Viral Infections

Following the discovery of plasmacytoid dendritic cells (pDCs) and of their extraordinary ability to produce type I IFNs (IFN-I) in response to TLR7 and TLR9 stimulation, it is assumed that their main function is to participate in the antiviral response. There is increasing evidence suggesting that pDCs and/or IFN-I can also have a detrimental role in a number of inflammatory and autoimmune diseases, in the context of chronic viral infections and in cancers. Whether these cells should be targeted in patients and how much of their biology is connected to IFN-I production remains unclear and is discussed here.

scholarly journals Lymphocytoid Choriomeningitis Virus Activates Plasmacytoid Dendritic Cells and Induces a Cytotoxic T-Cell Response via MyD88

2007 ◽  
Vol 82 (1) ◽  
pp. 196-206 ◽  
Author(s):  
Andreas Jung ◽  
Hiroki Kato ◽  
Yutaro Kumagai ◽  
Himanshu Kumar ◽  
Taro Kawai ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Intracellular Signaling ◽  
Plasmacytoid Dendritic Cells ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
Type I ◽  
Ctl Response ◽  
Type I Ifns ◽  
Lcmv Infection

ABSTRACTToll-like receptors (TLRs) and retinoic acid-inducible gene I-like helicases (RLHs) are two major machineries recognizing RNA virus infection of innate immune cells. Intracellular signaling for TLRs and RLHs is mediated by their cytoplasmic adaptors, i.e., MyD88 or TRIF and IPS-1, respectively. In the present study, we investigated the contributions of TLRs and RLHs to the cytotoxic T-lymphocyte (CTL) response by using lymphocytoid choriomeningitis virus (LCMV) as a model virus. The generation of virus-specific cytotoxic T lymphocytes was critically dependent on MyD88 but not on IPS-1. Type I interferons (IFNs) are known to be important for the development of the CTL response to LCMV infection. Serum levels of type I IFNs and proinflammatory cytokines were mainly dependent on the presence of MyD88, although IPS-1−/−mice showed a decrease in IFN-α levels but not in IFN-β and proinflammatory cytokine levels. Analysis ofIfna6+/GFPreporter mice revealed that plasmacytoid dendritic cells (DCs) are the major source of IFN-α in LCMV infection. MyD88−/−mice were highly susceptible to LCMV infection in vivo. These results suggest that recognition of LCMV by plasmacytoid DCs via TLRs is responsible for the production of type I IFNs in vivo. Furthermore, the activation of a MyD88-dependent innate mechanism induces a CTL response, which eventually leads to virus elimination.

scholarly journals Crosstalk between Dendritic Cells and Immune Modulatory Agents against Sepsis

Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 323 ◽  
Author(s):  
Guoying Wang ◽  
Xianghui Li ◽  
Lei Zhang ◽  
Abualgasim Elgaili Abdalla ◽  
Tieshan Teng ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Critical Role ◽  
Innate Immune ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Th2 Responses ◽  
Novel Strategy

Dendritic cells (DCs) play a critical role in the immune system which sense pathogens and present their antigens to prime the adaptive immune responses. As the progression of sepsis occurs, DCs are capable of orchestrating the aberrant innate immune response by sustaining the Th1/Th2 responses that are essential for host survival. Hence, an in-depth understanding of the characteristics of DCs would have a beneficial effect in overcoming the obstacle occurring in sepsis. This paper focuses on the role of DCs in the progression of sepsis and we also discuss the reverse sepsis-induced immunosuppression through manipulating the DC function. In addition, we highlight some potent immunotherapies that could be used as a novel strategy in the early treatment of sepsis.

scholarly journals Type I Interferons Mediate the Innate Cytokine Response to Recombinant Fowlpox Virus but Not the Induction of Plasmacytoid Dendritic Cell-Dependent Adaptive Immunity

2010 ◽  
Vol 84 (13) ◽  
pp. 6549-6563 ◽  
Author(s):  
Erin L. Lousberg ◽  
Cara K. Fraser ◽  
Michael G. Tovey ◽  
Kerrilyn R. Diener ◽  
John D. Hayball
Keyword(s):  
Immune Responses ◽  
Plasmacytoid Dendritic Cell ◽  
Type I Interferons ◽  
Interleukin 12 ◽  
Type I ◽  
Adaptive Immune Responses ◽  
Fowlpox Virus ◽  
Adaptive Immune ◽  
Type I Ifns

ABSTRACT Type I interferons (IFNs) are considered to be important mediators of innate immunity due to their inherent antiviral activity, ability to drive the transcription of a number of genes involved in viral clearance, and their role in the initiation of innate and adaptive immune responses. Due to the central role of type I IFNs, we sought to determine their importance in the generation of immunity to a recombinant vaccine vector fowlpox virus (FPV). In analyzing the role of type I IFNs in immunity to FPV, we show that they are critical to the secretion of a number of innate and proinflammatory cytokines, including type I IFNs themselves as well as interleukin-12 (IL-12), tumor necrosis factor-alpha (TNF-α), IL-6, and IL-1β, and that deficiency leads to enhanced virus-mediated antigen expression. Interestingly, however, type I IFNs were not required for adaptive immune responses to recombinant FPV even though plasmacytoid dendritic cells (pDCs), the primary producers of type I IFNs, have been shown to be requisite for this to occur. Furthermore, we provide evidence that the importance of pDCs may lie in their ability to capture and present virally derived antigen to T cells rather than in their capacity as professional type I IFN-producing cells.

scholarly journals Plasmacytoid Dendritic Cells Depletion and Elevation of IFN-γ Dependent Chemokines CXCL9 and CXCL10 in Children With Multisystem Inflammatory Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Francesca Caldarale ◽  
Mauro Giacomelli ◽  
Emirena Garrafa ◽  
Nicola Tamassia ◽  
Alessia Morreale ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Clinical Manifestations ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
Reactive Protein ◽  
Cardiovascular Damage ◽  
Inflammatory Chemokines ◽  
Ifn Γ ◽  
Inflammatory Syndrome

BackgroundSARS-CoV-2 occurs in the majority of children as COVID-19, without symptoms or with a paucisymptomatic respiratory syndrome, but a small proportion of children develop the systemic Multi Inflammatory Syndrome (MIS-C), characterized by persistent fever and systemic hyperinflammation, with some clinical features resembling Kawasaki Disease (KD).ObjectiveWith this study we aimed to shed new light on the pathogenesis of these two SARS-CoV-2-related clinical manifestations.MethodsWe investigated lymphocyte and dendritic cells subsets, chemokine/cytokine profiles and evaluated the neutrophil activity mediators, myeloperoxidase (MPO), and reactive oxygen species (ROS), in 10 children with COVID-19 and 9 with MIS-C at the time of hospital admission.ResultsPatients with MIS-C showed higher plasma levels of C reactive protein (CRP), MPO, IL-6, and of the pro-inflammatory chemokines CXCL8 and CCL2 than COVID-19 children. In addition, they displayed higher levels of the chemokines CXCL9 and CXCL10, mainly induced by IFN-γ. By contrast, we detected IFN-α in plasma of children with COVID-19, but not in patients with MIS-C. This observation was consistent with the increase of ISG15 and IFIT1 mRNAs in cells of COVID-19 patients, while ISG15 and IFIT1 mRNA were detected in MIS-C at levels comparable to healthy controls. Moreover, quantification of the number of plasmacytoid dendritic cells (pDCs), which constitute the main source of IFN-α, showed profound depletion of this subset in MIS-C, but not in COVID-19.ConclusionsOur results show a pattern of immune response which is suggestive of type I interferon activation in COVID-19 children, probably related to a recent interaction with the virus, while in MIS-C the immune response is characterized by elevation of the inflammatory cytokines/chemokines IL-6, CCL2, and CXCL8 and of the chemokines CXCL9 and CXL10, which are markers of an active Th1 type immune response. We believe that these immunological events, together with neutrophil activation, might be crucial in inducing the multisystem and cardiovascular damage observed in MIS-C.

scholarly journals Plasmacytoid Dendritic Cells: From Heart to Vessels

2010 ◽  
Vol 2010 ◽  
pp. 1-4 ◽  
Author(s):  
Rosalinda Sorrentino ◽  
Silvana Morello ◽  
Aldo Pinto
Keyword(s):  
Dendritic Cells ◽  
Cardiovascular Diseases ◽  
T Regulatory Cells ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
Regulatory Cells ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Stromal Component ◽  
Proinflammatory Responses

Cardiovascular diseases, formerly only attributed to the alterations of the stromal component, are now recognized as immune-based pathologies. Plasmacytoid Dendritic Cells (pDCs) are important immune orchestrators in heart and vessels. They highly produce IFN type I that promote the polarization of T cells towards a Th1 phenotype; however, pDCs can also participate to suppressive networks via the recruitment of T regulatory cells that downmodulate proinflammatory responses. pDCs populate the vessel wall layers during pathological conditions, such as atherosclerosis. It is thus clear that a better identification of pDCs activity in cardiovascular diseases can not only elucidate pathological mechanisms but also lead to new therapeutic approaches.

scholarly journals The role of myeloid receptors on murine plasmacytoid dendritic cells in induction of type I interferon

2011 ◽  
Vol 11 (7) ◽  
pp. 794-801 ◽  
Author(s):  
Rosalind E. Seeds ◽  
Subhankar Mukhopadhyay ◽  
Ian M. Jones ◽  
Siamon Gordon ◽  
Joanna L. Miller
Keyword(s):  
Dendritic Cells ◽  
Type I Interferon ◽  
Plasmacytoid Dendritic Cells ◽  
Type I

scholarly journals Non-Pathogenic Mopeia Virus Induces More Robust Activation of Plasmacytoid Dendritic Cells than Lassa Virus

Viruses ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 287 ◽  
Author(s):  
Justine Schaeffer ◽  
Stéphanie Reynard ◽  
Xavier Carnec ◽  
Natalia Pietrosemoli ◽  
Marie-Agnès Dillies ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Plasmacytoid Dendritic Cells ◽  
Health Concern ◽  
Lassa Virus ◽  
Type I ◽  
Viral Haemorrhagic Fever

Lassa virus (LASV) causes a viral haemorrhagic fever in humans and is a major public health concern in West Africa. An efficient immune response to LASV appears to rely on type I interferon (IFN-I) production and T-cell activation. We evaluated the response of plasmacytoid dendritic cells (pDC) to LASV, as they are an important and early source of IFN-I. We compared the response of primary human pDCs to LASV and Mopeia virus (MOPV), which is very closely related to LASV, but non-pathogenic. We showed that pDCs are not productively infected by either MOPV or LASV, but produce IFN-I. However, the activation of pDCs was more robust in response to MOPV than LASV. In vivo, pDC activation may support the control of viral replication through IFN-I production, but also improve the induction of a global immune response. Therefore, pDC activation could play a role in the control of LASV infection.

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