scholarly journals Antiviral Response by Plasmacytoid Dendritic Cells via Interferogenic Synapse with Infected Cells

2018 ◽  
Author(s):  
Sonia Assil ◽  
Séverin Coléon ◽  
Elodie Décembre ◽  
Lee Sherry ◽  
Omran Allatif ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Viral Infections ◽  
Antiviral Response ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
List Type ◽  
Toll Like Receptor ◽  
Actin Network ◽  
Infected Cells ◽  
Cell Interface

SummaryType I interferon (IFN-I) is critical for protection against viral infections. Plasmacytoid dendritic cells (pDCs) massively produce IFN-I against viruses. Physical contacts are required for pDC-mediated sensing of cells infected by genetically distant viruses. How and why these contacts are established remains enigmatic. Using dengue, hepatitis C, zika viruses, we demonstrate that the pDC/infected cell interface is a specialized platform for viral immunostimulatory-RNA transfer, which we named interferogenic synapse and required for pDC-mediated antiviral response. This synapse is an exquisitely differentiated territory with polarized adhesion complexes and regulators of actin network and endocytosis. Toll-like receptor 7-induced signaling in pDCs promotes the interferogenic synapse establishment, thus providing a feed-forward regulation that sustains contacts with infected cells. We propose that the interferogenic synapse is crucial to pDC function as it allows scanning of infected cells to locally secrete IFN-I at the infection site, thereby confining a response potentially deleterious to the host.HighlightspDCs adhere to infected cells via αLβ2 integrin/ICAM-1Regulators of actin network and endocytosis polarize at contactTLR7-induced signaling potentiates pDC polarityInfected cells activate pDCs by interferogenic synapse

scholarly journals SARS-CoV-2 infected cells trigger an acute antiviral response mediated by Plasmacytoid dendritic cells in mild but not severe COVID-19 patients

2021 ◽  
Author(s):  
Manon Venet ◽  
Margarida Sa Ribeiro ◽  
Elodie Décembre ◽  
Alicia Bellomo ◽  
Garima Joshi ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Antiviral Response ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
List Type ◽  
Viral Spread ◽  
Infected Cells ◽  
Specialized Function ◽  
Severity Of The Disease ◽  
Acute Antiviral Response

AbstractType I and III interferons (IFN-I/λ) are key antiviral mediators against SARS-CoV-2 infection. Here, we demonstrate that the plasmacytoid dendritic cells (pDCs) are predominant IFN-I/λ source by sensing SARS-CoV-2-infected cells. We show that sensing of viral RNA by pDCs requires sustained cell adhesion with infected cells. In turn, the pDCs restrict viral spread by a local IFN-I/λ response directed toward SARS-CoV-2-infected cells. This specialized function enables pDCs to efficiently turn-off viral replication, likely by a concentrated flux of antiviral effectors at the contact site with infected cells. Therefore, we propose that pDC activation is essential to locally control SARS-CoV-2-infection. By exploring the pDC response in patients, we further demonstrate that pDC responsiveness correlates with the severity of the disease and in particular that it is impaired in severe COVID-19 patients. Thus, the ability of pDCs to respond to SARS-CoV-2-infected cells could be a key to understand severe cases of COVID-19.HighlightspDCs are immune cells against SARS-CoV-2-infected cellspDC-mediated IFN-I/λ response against SARS-CoV-2 infected cells control COVID- 19 progressionpDC response by SARS-CoV-2 is restricted to IRF7-prioritized signaling leading to antiviral controlpDC antiviral response directed toward contacting SARS-CoV-2-infected cells

scholarly journals Human plasmacytoid dendritic cells mount a distinct antiviral response to virus-infected cells

2021 ◽  
Vol 6 (58) ◽  
pp. eabc7302
Author(s):  
Tae Jin Yun ◽  
Suzu Igarashi ◽  
Haoquan Zhao ◽  
Oriana A. Perez ◽  
Marcus R. Pereira ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Virus Detection ◽  
Plasmacytoid Dendritic Cells ◽  
Lung Epithelial Cells ◽  
Live Cells ◽  
Type I ◽  
Antiviral Immune Response ◽  
Lung Epithelial ◽  
Functional Consequences ◽  
Infected Cells

Plasmacytoid dendritic cells (pDCs) can rapidly produce interferons and other soluble factors in response to extracellular viruses or virus mimics such as CpG-containing DNA. pDCs can also recognize live cells infected with certain RNA viruses, but the relevance and functional consequences of such recognition remain unclear. We studied the response of primary DCs to the prototypical persistent DNA virus, human cytomegalovirus (CMV). Human pDCs produced high amounts of type I interferon (IFN-I) when incubated with live CMV-infected fibroblasts but not with free CMV; the response involved integrin-mediated adhesion, transfer of DNA-containing virions to pDCs, and the recognition of DNA through TLR9. Compared with transient polyfunctional responses to CpG or free influenza virus, pDC response to CMV-infected cells was long-lasting, dominated by the production of IFN-I and IFN-III, and lacked diversification into functionally distinct populations. Similarly, pDC activation by influenza-infected lung epithelial cells was highly efficient, prolonged, and dominated by interferon production. Prolonged pDC activation by CMV-infected cells facilitated the activation of natural killer cells critical for CMV control. Last, patients with CMV viremia harbored phenotypically activated pDCs and increased circulating IFN-I and IFN-III. Thus, recognition of live infected cells is a mechanism of virus detection by pDCs that elicits a unique antiviral immune response.

scholarly journals Efficient Virus Assembly, but Not Infectivity, Determines the Magnitude of Hepatitis C Virus-Induced Interferon Alpha Responses of Plasmacytoid Dendritic Cells

2014 ◽  
Vol 89 (6) ◽  
pp. 3200-3208 ◽  
Author(s):  
Elena Grabski ◽  
Ilka Wappler ◽  
Stephanie Pfaender ◽  
Eike Steinmann ◽  
Sibylle Haid ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Core Protein ◽  
Virus Assembly ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
Hepatitis C Virus Infection ◽  
Infected Cells ◽  
Interferon Responses

ABSTRACTWorldwide, approximately 160 million people are chronically infected with hepatitis C virus (HCV), seven distinct genotypes of which are discriminated. The hallmarks of HCV are its genetic variability and the divergent courses of hepatitis C progression in patients. We assessed whether intragenotypic HCV variations would differentially trigger host innate immunity. To this end, we stimulated human primary plasmacytoid dendritic cells (pDC) with crude preparations of different cell culture-derived genotype 2a HCV variants. Parental Japanese fulminant hepatitis C virus (JFH1) did not induce interferon alpha (IFN-α), whereas the intragenotypic chimera Jc1 triggered massive IFN-α responses. Purified Jc1 retained full infectivity but no longer induced IFN-α. Coculture of pDC with HCV-infected hepatoma cells retrieved the capacity to induce IFN-α, whereas Jc1-infected cells triggered stronger responses than JFH1-infected cells. Since the infectivity of virus particles did not seem to affect pDC activation, we next tested Jc1 mutants that were arrested at different stages of particle assembly. These experiments revealed that efficient assembly and core protein envelopment were critically needed to trigger IFN-α. Of note, sequences within domain 2 of the core that vitally affect virus assembly also crucially influenced the IFN-α responses of pDC. These data showed that viral determinants shaped host innate IFN-α responses to HCV.IMPORTANCEAlthough pegylated IFN-α plus ribavirin currently is the standard of care for the treatment of chronic hepatitis C virus infection, not much is known about the relevance of early interferon responses in the pathogenesis of hepatitis C virus infection. Here, we addressed whether intragenotypic variations of hepatitis C virus would account for differential induction of type I interferon responses mounted by primary blood-derived plasmacytoid dendritic cells. Surprisingly, a chimeric genotype 2a virus carrying the nonstructural genes of Japanese fulminant hepatitis C virus (JFH1) induced massive type I interferon responses, whereas the original genotype 2a JFH1 strain did not. Our detailed analyses revealed that, not the virus infectivity, but rather, the efficiency of virus assembly and core protein envelopment critically determined the magnitude of interferon responses. To our knowledge, this is the first example of hepatitis C virus-associated genetic variations that determine the magnitude of innate host responses.

scholarly journals Regulation of TLR7/9 responses in plasmacytoid dendritic cells by BST2 and ILT7 receptor interaction

2009 ◽  
Vol 206 (7) ◽  
pp. 1603-1614 ◽  
Author(s):  
Wei Cao ◽  
Laura Bover ◽  
Minkwon Cho ◽  
Xiaoxia Wen ◽  
Shino Hanabuchi ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Proinflammatory Cytokines ◽  
Stromal Cell ◽  
Bone Marrow Stromal Cell ◽  
Type I Interferon ◽  
Plasmacytoid Dendritic Cells ◽  
Orphan Receptor ◽  
Receptor Interaction ◽  
Type I ◽  
Toll Like Receptor

Plasmacytoid dendritic cells (pDCs) produce copious type I interferon (IFN) upon sensing nucleic acids through Toll-like receptor (TLR) 7 and TLR9. Uncontrolled pDC activation and IFN production are implicated in lymphopenia and autoimmune diseases; therefore, a mechanism controlling pDC IFN production is essential. Human pDCs specifically express an orphan receptor, immunoglobulin-like transcript 7 (ILT7). Here, we discovered an ILT7 ligand expressed by human cell lines and identified it as bone marrow stromal cell antigen 2 (BST2; CD317). BST2 directly binds to purified ILT7 protein, initiates signaling via the ILT7–FcεRIγ complex, and strongly inhibits production of IFN and proinflammatory cytokines by pDCs. Readily induced by IFN and other proinflammatory cytokines, BST2 may modulate the human pDC’s IFN responses through ILT7 in a negative feedback fashion.

scholarly journals Toll-like receptor–mediated induction of type I interferon in plasmacytoid dendritic cells requires the rapamycin-sensitive PI(3)K-mTOR-p70S6K pathway

2008 ◽  
Vol 9 (10) ◽  
pp. 1157-1164 ◽  
Author(s):  
Weiping Cao ◽  
Santhakumar Manicassamy ◽  
Hua Tang ◽  
Sudhir Pai Kasturi ◽  
Ali Pirani ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Type I Interferon ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
Toll Like Receptor

Plasmacytoid dendritic cells and autoimmune inflammation

2014 ◽  
Vol 395 (3) ◽  
pp. 335-346 ◽  
Author(s):  
Georgina Galicia ◽  
Jennifer L. Gommerman
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
Toll Like Receptor ◽  
Autoimmune Encephalomyelitis ◽  
Effector Cells ◽  
The Central Nervous System ◽  
Antigen Presenting ◽  
Experimental Autoimmune

Abstract Plasmacytoid dendritic cells (pDC) are a sub-population of dendritic cells (DC) that produce large amounts of type I interferon (IFN) in response to nucleic acids that bind and activate toll-like-receptor (TLR)9 and TLR7. Type I IFN can regulate the function of B, T, DC, and natural killer (NK) cells and can also alter the residence time of leukocytes within lymph nodes. Activated pDC can also function as antigen presenting cells (APC) and have the potential to prime and differentiate T cells into regulatory or inflammatory effector cells, depending on the context. In this review we discuss pDC ontogeny, function, trafficking, and activation. We will also examine how pDC can potentially be involved in regulating immune responses in the periphery as well as within the central nervous system (CNS) during multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE).

scholarly journals Antiviral Protein Viperin Promotes Toll-like Receptor 7- and Toll-like Receptor 9-Mediated Type I Interferon Production in Plasmacytoid Dendritic Cells

Immunity ◽  
2011 ◽  
Vol 34 (3) ◽  
pp. 352-363 ◽  
Author(s):  
Tatsuya Saitoh ◽  
Takashi Satoh ◽  
Naoki Yamamoto ◽  
Satoshi Uematsu ◽  
Osamu Takeuchi ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Type I Interferon ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
Interferon Production ◽  
Toll Like Receptor ◽  
Antiviral Protein

scholarly journals Sensing of Immature Particles Produced by Dengue Virus Infected Cells Induces an Antiviral Response by Plasmacytoid Dendritic Cells

2014 ◽  
Vol 10 (10) ◽  
pp. e1004434 ◽  
Author(s):  
Elodie Décembre ◽  
Sonia Assil ◽  
Marine L. B. Hillaire ◽  
Wanwisa Dejnirattisai ◽  
Juthathip Mongkolsapaya ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Dengue Virus ◽  
Antiviral Response ◽  
Plasmacytoid Dendritic Cells ◽  
Infected Cells
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