scholarly journals Inhibition of the Type I Interferon Response in Human Dendritic Cells by Dengue Virus Infection Requires a Catalytically Active NS2B3 Complex

2010 ◽  
Vol 84 (19) ◽  
pp. 9760-9774 ◽  
Author(s):  
Juan R. Rodriguez-Madoz ◽  
Alan Belicha-Villanueva ◽  
Dabeiba Bernal-Rubio ◽  
Joseph Ashour ◽  
Juan Ayllon ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Dengue Virus ◽  
Type I Interferon ◽  
Poly I:C ◽  
Interferon Response ◽  
Type I ◽  
Type I Ifn ◽  
Human Virus ◽  
Catalytically Active ◽  
Human Dendritic Cells

ABSTRACT Dengue virus (DENV) is the most prevalent arthropod-borne human virus, able to infect and replicate in human dendritic cells (DCs), inducing their activation and the production of proinflammatory cytokines. However, DENV can successfully evade the immune response in order to produce disease in humans. Several mechanisms of immune evasion have been suggested for DENV, most of them involving interference with type I interferon (IFN) signaling. We recently reported that DENV infection of human DCs does not induce type I IFN production by those infected DCs, impairing their ability to prime naive T cells toward Th1 immunity. In this article, we report that DENV also reduces the ability of DCs to produce type I IFN in response to several inducers, such as infection with other viruses or exposure to Toll-like receptor (TLR) ligands, indicating that DENV antagonizes the type I IFN production pathway in human DCs. DENV-infected human DCs showed a reduced type I IFN response to Newcastle disease virus (NDV), Sendai virus (SeV), and Semliki Forest virus (SFV) infection and to the TLR3 agonist poly(I:C). This inhibitory effect is DENV dose dependent, requires DENV replication, and takes place in DENV-infected DCs as early as 2 h after infection. Expressing individual proteins of DENV in the presence of an IFN-α/β production inducer reveals that a catalytically active viral protease complex is required to reduce type I IFN production significantly. These results provide a new mechanism by which DENV evades the immune system in humans.

scholarly journals Dengue Virus Inhibits the Production of Type I Interferon in Primary Human Dendritic Cells

2011 ◽  
Vol 85 (6) ◽  
pp. 3042-3042
Author(s):  
J. R. Rodriguez-Madoz ◽  
D. Bernal-Rubio ◽  
D. Kaminski ◽  
K. Boyd ◽  
A. Fernandez-Sesma
Keyword(s):  
Dendritic Cells ◽  
Dengue Virus ◽  
Type I Interferon ◽  
Type I ◽  
Human Dendritic Cells

scholarly journals Selective blockade of the inhibitory Fcγ receptor (FcγRIIB) in human dendritic cells and monocytes induces a type I interferon response program

2007 ◽  
Vol 204 (10) ◽  
pp. 2489-2489 ◽  
Author(s):  
Kavita M. Dhodapkar ◽  
Devi Banerjee ◽  
John Connolly ◽  
Anjli Kukreja ◽  
Elyana Matayeva ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Type I Interferon ◽  
Interferon Response ◽  
Type I ◽  
Fcγ Receptor ◽  
Selective Blockade ◽  
Human Dendritic Cells

scholarly journals Selective blockade of the inhibitory Fcγ receptor (FcγRIIB) in human dendritic cells and monocytes induces a type I interferon response program

2007 ◽  
Vol 204 (10) ◽  
pp. 2494-2494
Author(s):  
Kavita M. Dhodapkar ◽  
Devi Banerjee ◽  
John Connolly ◽  
Anjli Kukreja ◽  
Elyana Matayeva ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Type I Interferon ◽  
Interferon Response ◽  
Type I ◽  
Fcγ Receptor ◽  
Selective Blockade ◽  
Human Dendritic Cells

scholarly journals Dengue Virus Inhibits the Production of Type I Interferon in Primary Human Dendritic Cells

2010 ◽  
Vol 84 (9) ◽  
pp. 4845-4850 ◽  
Author(s):  
Juan R. Rodriguez-Madoz ◽  
Dabeiba Bernal-Rubio ◽  
Dorota Kaminski ◽  
Kelley Boyd ◽  
Ana Fernandez-Sesma
Keyword(s):  
Dendritic Cells ◽  
Dengue Virus ◽  
Type I Interferon ◽  
Productive Infection ◽  
Type I ◽  
Human Immune ◽  
Alpha Beta ◽  
Human Dendritic Cells

ABSTRACT Dengue virus (DENV) infects human immune cells in vitro and likely infects dendritic cells (DCs) in vivo. DENV-2 productive infection induces activation and release of high levels of chemokines and proinflammatory cytokines in monocyte-derived DCs (moDCs), with the notable exception of alpha/beta interferon (IFN-α/β). Interestingly, DENV-2-infected moDCs fail to prime T cells, most likely due to the lack of IFN-α/β released by moDCs, since this effect was reversed by addition of exogenous IFN-β. Together, our data show that inhibition of IFN-α/β production by DENV in primary human moDCs is a novel mechanism of immune evasion.

PLASMACYTOID DENDRITIC CELLS FUNCTION IN HIV INFECTION

2008 ◽  
Vol 31 (4) ◽  
pp. 13
Author(s):  
Martin Hyrcza ◽  
Mario Ostrowski ◽  
Sandy Der
Keyword(s):  
Dendritic Cells ◽  
Influenza Virus ◽  
Hiv Infection ◽  
Gene Transcription ◽  
Sendai Virus ◽  
Plasmacytoid Dendritic Cells ◽  
Type I Interferons ◽  
Interferon Response ◽  
Type I ◽  
Type I Ifn

Plasmacytoid dendritic cells (pDCs) are innate immune cells able to produce large quantities of type I interferons (IFN) when activated. Human immunodeficiency virus (HIV)-infected patients show generalized immune dysfunction characterized in part by chronic interferon response. In this study we investigated the role of dendritic cells inactivating and maintaining this response. Specifically we compared the IFN geneactivity in pDCs in response to several viruses and TLR agonists. We hypothesized that 1) the pattern of IFN gene transcription would differ in pDCs treated with HIV than with other agents, and 2) that pDCs from patients from different stages of disease would respond differently to the stimulations. To test these hypotheses, we obtained pDCs from 15 HIV-infected and uninfected individuals and treated freshly isolated pDCs with either HIV (BAL strain), influenza virus (A/PR/8/34), Sendai virus (Cantell strain), TLR7 agonist(imiquimod), or TLR9 agonist (CpG-ODN) for 6h. Type I IFN gene transcription was monitored by real time qPCRfor IFNA1, A2, A5, A6, A8,A17, B1, and E1, and cytokine levels were assayed by Cytometric Bead Arrays forTNF?, IL6, IL8, IL10, IL1?, and IL12p70. pDC function as determined by these two assays showed no difference between HIV-infected and uninfected patients or between patients with early or chronic infection. Specifically, HIV did notinduce type I IFN gene expression, whereas influenza virus, Sendai virus and imiquimod did. Similarly, HIV failed to induce any cytokine release from pDCs in contrast to influenza virus, Sendai virus and imiquimod, which stimulatedrelease of TNF?, IL6, or IL8. Together these results suggest that the reaction of pDCs to HIV virus is quantitatively different from the response to agents such as virus, Sendai virus, and imiquimod. In addition, pDCs from HIV-infected persons have responses similar to pDCs from uninfected donors, suggesting, that the DC function may not be affected by HIV infection.

scholarly journals Regulatory NLRs Control the RLR-Mediated Type I Interferon and Inflammatory Responses in Human Dendritic Cells

2018 ◽  
Vol 9 ◽  
Author(s):  
Tünde Fekete ◽  
Dora Bencze ◽  
Attila Szabo ◽  
Eszter Csoma ◽  
Tamas Biro ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Inflammatory Responses ◽  
Type I Interferon ◽  
Type I ◽  
Human Dendritic Cells

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.

Sign in / Sign up

Export Citation Format

Share Document