scholarly journals Toll-like Receptor 9–mediated Recognition of Herpes Simplex Virus-2 by Plasmacytoid Dendritic Cells

2003 ◽  
Vol 198 (3) ◽  
pp. 513-520 ◽  
Author(s):  
Jennifer Lund ◽  
Ayuko Sato ◽  
Shizuo Akira ◽  
Ruslan Medzhitov ◽  
Akiko Iwasaki
Keyword(s):  
Dendritic Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Plasmacytoid Dendritic Cells ◽  
Endocytic Pathway ◽  
Type I ◽  
Dependent Manner ◽  
Toll Like Receptor ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2

Plasmacytoid dendritic cells (pDCs) have been identified as a potent secretor of the type I interferons (IFNs) in response to CpG as well as several viruses. In this study, we examined the molecular mechanism of virus recognition by pDCs. First, we demonstrated that the CD11c+Gr-1intB220+ pDCs from mouse bone marrow secreted high levels of IFN-α in response to either live or UV-inactivated Herpes simplex virus-2 (HSV-2). Next, we identified that IFN-α secretion by pDCs required the expression of the adaptor molecule MyD88, suggesting the involvement of a Toll-like receptor (TLR) in HSV-2 recognition. To test whether a TLR mediates HSV-2–induced IFN-α secretion from pDCs, various knockout mice were examined. These experiments revealed a clear requirement for TLR9 in this process. Further, we demonstrated that purified HSV-2 DNA can trigger IFN-α secretion from pDCs and that inhibitory CpG oligonucleotide treatment diminished HSV-induced IFN-α secretion by pDCs in a dose-dependent manner. The recognition of HSV-2 by TLR9 was mediated through an endocytic pathway that was inhibited by chloroquine or bafilomycin A1. The strict requirement for TLR9 in IFN-α secretion was further confirmed by the inoculation of HSV-2 in vivo. Therefore, these results demonstrate a novel mechanism whereby the genomic DNA of a virus can engage TLR9 and result in the secretion of IFN-α by pDCs.

scholarly journals Role of CD123 (+) Plasmacytoid Dendritic Cells in Etiologically Different Variants of Erythema Multiforme: A Monocentric Retrospective Study

2021 ◽  
Vol 8 (2) ◽  
pp. 89-96
Author(s):  
Hatice B. Zengin ◽  
Tatsiana Pukhalskaya ◽  
Bruce R. Smoller
Keyword(s):  
Dendritic Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Erythema Multiforme ◽  
Inflammatory Infiltrate ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
A Cell ◽  
Skin Conditions ◽  
Simplex Virus

Plasmacytoid dendritic cells (pDCs) constitute a subset of dendritic cells known to be the “professional” interferon type I (IFN-I) producers. pDCs play an important role in antiviral immunity, as well as linking innate and adaptive immunity. Under normal conditions pDCs are not present in skin. They are shown to be a part of the inflammatory infiltrate in different skin conditions including erythema multiforme (EM). This condition is considered to be a cell-mediated immune reaction to a wide variety of agents, most commonly herpes simplex virus. Nevertheless, the pathophysiology of EM still remains unclear. In this study, we grouped 32 biopsies from 30 patients diagnosed with EM, based on their etiology and analyzed the density and distribution of CD123 positive pDCs. In all cases we observed a greatly increased number of pDCs in the dermal inflammatory infiltrate. Virally-induced EM (by herpes simplex virus (HSV) and other viruses) was more likely to have a significantly higher number of pDCs compared to non-virally associated EM. Hence, we think that pDCs play a key role in the pathogenesis of EM independent of etiology and may play an increased role in virally-associated cases. Further studies on pDCs would clarify their importance in EM and improve our understanding of the pathophysiology of this disease.

scholarly journals Herpes simplex virus type I (HSV-1) replicates in mature dendritic cells but can only be transferred in a cell-cell contact-dependent manner

2011 ◽  
Vol 89 (6) ◽  
pp. 973-979 ◽  
Author(s):  
Andreas Goldwich ◽  
Alexander T. Prechtel ◽  
Petra Mühl-Zürbes ◽  
Nadine M. Pangratz ◽  
Hella Stössel ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Cell Contact ◽  
Type I ◽  
Dependent Manner ◽  
A Cell ◽  
Simplex Virus

scholarly journals Role for Plasmacytoid Dendritic Cells in the Immune Control of Recurrent Human Herpes Simplex Virus Infection

2008 ◽  
Vol 83 (4) ◽  
pp. 1952-1961 ◽  
Author(s):  
Heather Donaghy ◽  
Lidija Bosnjak ◽  
Andrew N. Harman ◽  
Valerie Marsden ◽  
Stephen K. Tyring ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Infection ◽  
Plasmacytoid Dendritic Cells ◽  
Immune Control ◽  
T Lymphocyte Proliferation ◽  
Simplex Virus

ABSTRACT Plasmacytoid dendritic cells (pDC) are an important component of the innate immune response, producing large amounts of alpha interferon in response to viral stimulation in vitro. Under noninflammatory conditions, pDC are not found in the skin and are restricted in location to the blood and lymph nodes. Therefore, their role in mucosal and cutaneous herpes simplex virus (HSV) infection has not been well-defined. In this study we show a role for human pDC in the immune response to HSV infection. First, by confocal microscopy we showed that pDC infiltrate the dermis of recurrent genital herpes simplex lesions at early and late phases, often at the dermo-epidermal junction. We then showed that pDC in vitro are resistant to HSV infection despite expressing the entry receptors CD111, CD112, and HVE-A. Within the lesions, pDC were found closely associated with CD3+ lymphocytes and NK cells, especially those which were activated (CD69+). Furthermore, these HSV-exposed pDC were able to stimulate virus-specific autologous T-lymphocyte proliferation. We conclude from this work that pDC may contribute to the immune control of recurrent herpes virus infection in vivo.

Herpes simplex virus type I infection of mature dendritic cells leads to reduced LMP7-mRNA-expression levels

Immunobiology ◽  
2009 ◽  
Vol 214 (9-10) ◽  
pp. 861-867 ◽  
Author(s):  
Jutta Eisemann ◽  
Alexander T. Prechtel ◽  
Petra Mühl-Zürbes ◽  
Alexander Steinkasserer ◽  
Mirko Kummer
Keyword(s):  
Dendritic Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Mrna Expression ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Type I ◽  
Expression Levels ◽  
Simplex Virus ◽  
Mrna Expression Levels

The US3 kinase of Herpes Simplex virus phosphorylates the RNA sensor RIG-I to suppress innate immunity

2021 ◽  
Author(s):  
Michiel van Gent ◽  
Jessica J. Chiang ◽  
Santoshi Muppala ◽  
Cindy Chiang ◽  
Walid Azab ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Immune Escape ◽  
Type I ◽  
Dependent Manner ◽  
Herpes Simplex Virus 1 ◽  
E3 Ligases ◽  
Immune Evasion Mechanism ◽  
Simplex Virus ◽  
Hsv 1

Recent studies demonstrated that the signaling activity of the cytosolic pathogen sensor retinoic acid-inducible gene-I (RIG-I) is modulated by a variety of post-translational modifications (PTMs) to fine-tune the antiviral type I interferon (IFN) response. Whereas K63-linked ubiquitination of the RIG-I caspase activation and recruitment domains (CARDs) catalyzed by TRIM25 or other E3 ligases activates RIG-I, phosphorylation of RIG-I at S8 and T170 represses RIG-I signal transduction by preventing the TRIM25-RIG-I interaction and subsequent RIG-I ubiquitination. While strategies to suppress RIG-I signaling by interfering with its K63-polyubiquitin-dependent activation have been identified for several viruses, evasion mechanisms that directly promote RIG-I phosphorylation to escape antiviral immunity are unknown. Here, we show that the serine/threonine (Ser/Thr) kinase US3 of herpes simplex virus 1 (HSV-1) binds to RIG-I and phosphorylates RIG-I specifically at S8. US3-mediated phosphorylation suppressed TRIM25-mediated RIG-I ubiquitination, RIG-I-MAVS binding, and type I IFN induction. We constructed a mutant HSV-1 encoding a catalytically-inactive US3 protein (K220A) and found that, in contrast to the parental virus, the US3 mutant HSV-1 is unable to phosphorylate RIG-I at S8 and elicited higher levels of type I IFNs, IFN-stimulated genes (ISGs), and proinflammatory cytokines in a RIG-I-dependent manner. Finally, we show that this RIG-I evasion mechanism is conserved among the alphaherpesvirus US3 kinase family. Collectively, our study reveals a novel immune evasion mechanism of herpesviruses in which their US3 kinases phosphorylate the sensor RIG-I to keep it in the signaling-repressed state. IMPORTANCE Herpes simplex virus 1 (HSV-1) establishes life-long latency in the majority of the human population worldwide. HSV-1 occasionally reactivates to produce infectious virus and to facilitate dissemination. While often remaining subclinical, both primary infection and reactivation occasionally cause debilitating eye diseases, which can lead to blindness, as well as life-threatening encephalitis and newborn infections. To identify new therapeutic targets for HSV-1-induced diseases, it is important to understand the HSV-1-host interactions that may influence infection outcome and disease. Our work uncovered direct phosphorylation of the pathogen sensor RIG-I by alphaherpesvirus-encoded kinases as a novel viral immune escape strategy and also underscores the importance of RNA sensors in surveilling DNA virus infection.

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