scholarly journals Plasmacytoid Dendritic Cells Contribute to the Production of IFN-β via TLR7-MyD88-Dependent Pathway and CTL Priming during Respiratory Syncytial Virus Infection

Viruses ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 730 ◽  
Author(s):  
Tae Hoon Kim ◽  
Dong Sun Oh ◽  
Hi Eun Jung ◽  
Jun Chang ◽  
Heung Kyu Lee
Keyword(s):  
Dendritic Cells ◽  
Respiratory Syncytial Virus ◽  
Type I Interferon ◽  
Yellow Fluorescent Protein ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
Antigen Specificity ◽  
Interferon Β ◽  
Rsv Infection ◽  
Syncytial Virus

Respiratory syncytial virus (RSV) is the leading cause of respiratory viral infection in infants and children, yet little is known about the antiviral response of plasmacytoid dendritic cells (pDCs) to RSV infection. We tracked the cellular source of interferon-β using interferon-β/yellow fluorescent protein (YFP) reporter mice and identified the signaling pathway activated by RSV that induces type I interferon production in pDCs and DCs. Results from in vitro analyses of RSV-stimulated bone marrow cells revealed that RSV induces interferon-β production in both pDCs and DCs. Kinetic analyses of interferon-β-producing cells in RSV-infected lung cells in vivo indicated that pDCs are rapidly recruited to sites of inflammation during infection. These cells produced interferon-β via the TLR7-MyD88-mediated pathway and IFNα1R-mediated pathway rather than the MAVS-mediated pathway. Moreover, pDC-ablated mice exhibited decreased interferon-γ production and the antigen specificity of CD8+ T cells. Collectively, these data indicate that pDCs play pivotal roles in cytotoxic T lymphocyte (CTL) responses and are one of producers of type I interferon during RSV infection.

scholarly journals Lack of Type I Interferon Signaling Ameliorates Respiratory Syncytial Virus-Induced Lung Inflammation and Restores Antioxidant Defenses

Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 67
Author(s):  
Maria Ansar ◽  
Yue Qu ◽  
Teodora Ivanciuc ◽  
Roberto P. Garofalo ◽  
Antonella Casola
Keyword(s):  
Respiratory Syncytial Virus ◽  
Airway Inflammation ◽  
Type I Interferon ◽  
Cell Model ◽  
Antioxidant Defenses ◽  
Related Factor ◽  
Type I ◽  
Type I Ifn ◽  
Rsv Infection ◽  
Syncytial Virus

Respiratory syncytial virus (RSV) infection in mouse and human lung is associated with pathogenic inflammation and oxidative injury. RSV impairs antioxidant responses by increasing the degradation of transcription factor NF-E2-related factor 2 (NRF2), which controls the expression of several antioxidant enzymes (AOEs). In addition to its protective effects, type I IFNs have been increasingly recognized as important mediators of host pathogenic responses during acute respiratory viral infections. We used a mouse model of RSV infection to investigate the effect of lack of type I interferon (IFN) receptor on viral-mediated clinical disease, airway inflammation, NRF2 expression, and antioxidant defenses. In the absence of type I IFN signaling, RSV-infected mice showed significantly less body weight loss and airway obstruction, as well as a significant reduction in cytokine and chemokine secretion and airway inflammation. Lack of type I IFN receptor was associated with greatly reduced virus-induced promyelocytic leukemia lung protein expression, which we showed to be necessary for virus-induced NRF2 degradation in a cell model of infection, resulting in restoration of NRF2 levels, AOE expression, and airway antioxidant capacity. Our data support the concept that modulation of type I IFN production and/or signaling could represent an important therapeutic strategy to ameliorate severity of RSV-induced lung disease.

scholarly journals Differential Role of Anti-Viral Sensing Pathway for the Production of Type I Interferon β in Dendritic Cells and Macrophages Against Respiratory Syncytial Virus A2 Strain Infection

Viruses ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 62 ◽  
Author(s):  
Dong Oh ◽  
Tae Kim ◽  
Heung Lee
Keyword(s):  
Dendritic Cells ◽  
Respiratory Syncytial Virus ◽  
Primary Response ◽  
Type I Interferons ◽  
Type I ◽  
Type I Ifns ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Mitochondrial Antiviral Signaling

Respiratory syncytial virus (RSV) is a major cause of respiratory infectious disease in infants and young children. Dendritic cells (DCs) and macrophages (MACs) are known to play important roles in RSV recognition, and in the production of type I interferons (IFNs) and pro-inflammatory cytokine in RSV infection. Toll-like receptor 7 (TLR7), myeloid differentiation primary response 88 (MyD88), and mitochondrial antiviral-signaling protein (MAVS) are known to be important for the RSV sensing pathway in DCs and MACs. However, despite the critical roles of type I IFNs in the anti-RSV immune response, the pattern recognition receptors (PRRs) that are required for RSV sensing in DCs and MACs remain unclear. Here, we investigate the pathway activated by RSV A2 strain infection using an IFN-β/YFP reporter mouse model to visualize IFN-β-producing cells and in vitro RSV infection in bone marrow-derived DCs (BM-DCs) and macrophages (BM-DMs). We present our finding that MyD88, but not TLR7, are important for RSV recognition and type I IFN and pro-inflammatory production in DCs and MACs. MAVS-deficient BM-DCs and BM-DMs show impaired induction of IFN-β production upon RSV stimulation, and this effect is RSV replication-dependent. Our study provides information on cell type-specific PRR requirements in innate immune responses against RSV infection.

scholarly journals Plasmacytoid dendritic cells inhibit pulmonary immunopathology and promote clearance of respiratory syncytial virus

2006 ◽  
Vol 203 (5) ◽  
pp. 1153-1159 ◽  
Author(s):  
Joost J. Smit ◽  
Brian D. Rudd ◽  
Nicholas W. Lukacs
Keyword(s):  
Dendritic Cells ◽  
Respiratory Syncytial Virus ◽  
Dendritic Cell ◽  
Immune Responses ◽  
Plasmacytoid Dendritic Cell ◽  
Protective Role ◽  
Plasmacytoid Dendritic Cells ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Acquired Immune Responses

Respiratory syncytial virus (RSV) infection is widely spread and is a major cause of bronchiolitis in infants and high-risk adults, often leading to hospitalization. RSV infection leads to obstruction and inflammation of the airways and induction of innate and acquired immune responses. Because dendritic cells (DCs) are essential in the elicitation of these immune responses, we investigated the presence and the role of dendritic cell subtypes upon RSV infection in the lung. Here, we report that RSV infection increased the number of both conventional and plasmacytoid dendritic cells in the lung and the lung-draining lymph nodes. In particular, the increase in plasmacytoid dendritic cell numbers was sustained and lasted until 30 d after infection. Depletion of plasmacytoid dendritic cells resulted in decreased RSV clearance. In addition, depletion of plasmacytoid dendritic cells resulted in an exacerbation of all manifestations of immune-mediated pathology caused by RSV infection. In conclusion, this study demonstrates that both conventional and plasmacytoid dendritic cells are attracted to the site of RSV infection. It is demonstrated that plasmacytoid dendritic cells play a protective role during RSV infection by modulation of local immune responses.

scholarly journals Type I Interferon Inhibition and Dendritic Cell Activation during Gammaherpesvirus Respiratory Infection

2007 ◽  
Vol 81 (18) ◽  
pp. 9778-9789 ◽  
Author(s):  
Janet L. Weslow-Schmidt ◽  
Nancy A. Jewell ◽  
Sara E. Mertz ◽  
J. Pedro Simas ◽  
Joan E. Durbin ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Cell Activation ◽  
Type I Interferon ◽  
Plasmacytoid Dendritic Cells ◽  
The Body ◽  
Type I ◽  
Type I Ifn ◽  
Dendritic Cell Activation ◽  
Murine Gammaherpesvirus

ABSTRACT The respiratory tract is a major mucosal site for microorganism entry into the body, and type I interferon (IFN) and dendritic cells constitute a first line of defense against viral infections. We have analyzed the interaction between a model DNA virus, plasmacytoid dendritic cells, and type I IFN during lung infection of mice. Our data show that murine gammaherpesvirus 68 (γHV68) inhibits type I IFN secretion by dendritic cells and that plasmacytoid dendritic cells are necessary for conventional dendritic cell maturation in response to γHV68. Following γHV68 intranasal inoculation, the local and systemic IFN-α/β response is below detectable levels, and plasmacytoid dendritic cells are activated and recruited into the lung with a tissue distribution that differs from that of conventional dendritic cells. Our results suggest that plasmacytoid dendritic cells and type I IFN have important but independent roles during the early response to a respiratory γHV68 infection. γHV68 infection inhibits type I IFN production by dendritic cells and is a poor inducer of IFN-α/β in vivo, which may serve as an immune evasion strategy.

scholarly journals Human cytomegalovirus suppresses type I interferon secretion by plasmacytoid dendritic cells through its interleukin 10 homolog

Virology ◽  
2009 ◽  
Vol 390 (2) ◽  
pp. 330-337 ◽  
Author(s):  
W.L. William Chang ◽  
Peter A. Barry ◽  
Richard Szubin ◽  
Dai Wang ◽  
Nicole Baumgarth
Keyword(s):  
Dendritic Cells ◽  
Human Cytomegalovirus ◽  
Type I Interferon ◽  
Interleukin 10 ◽  
Plasmacytoid Dendritic Cells ◽  
Type I

scholarly journals Mesenchymal Stem Cells Alleviate Moderate-to-Severe Psoriasis by Reducing the Production of Type I Interferon (IFN-I) by Plasmacytoid Dendritic Cells (pDCs)

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Maosheng Chen ◽  
Jing Peng ◽  
Qi Xie ◽  
Na Xiao ◽  
Xian Su ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Dendritic Cells ◽  
Type I Interferon ◽  
Neutrophil Function ◽  
Plasmacytoid Dendritic Cells ◽  
Human Umbilical Cord ◽  
Therapeutic Effects ◽  
Type I ◽  
Cytokines And Chemokines

The anti-inflammatory and immunomodulatory properties of mesenchymal stem cells (MSCs) have been proposed to be involved in some autoimmune diseases and have been successfully tested in patients and mice. But their contribution to psoriasis and the underlying mechanisms involved remains elusive. Here, we explored the feasibility of using human umbilical cord-derived MSC (hUC-MSC) infusion as a therapeutic approach in an imiquimod- (IMQ-) induced psoriasis mouse model. MSC infusion were found to significantly reduce the severity and development of psoriasis, inhibit the infiltration of immune cells to the skin, and downregulate the expression of several proinflammatory cytokines and chemokines. Our results provide an explanation for the therapeutic effects of MSC infusion by first suppressing neutrophil function and then downregulating the production of type I interferon (IFN-I) by plasmacytoid dendritic cells (pDCs). Therefore, we discovered a novel mechanism of stem cell therapy for psoriasis. In summary, our results showed that MSC infusion could be an effective and safe treatment for psoriasis.

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