Special Issue "Dendritic Cells and Antiviral Defense"

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Antivirals & Vaccines".

Deadline for manuscript submissions: closed (15 November 2019).

Special Issue Editors

Dr. Simon M. Barratt-Boyes
Website
Guest Editor
University of Pittsburgh, Pittsburgh, PA 15261, USA
Interests: vaccination and therapy for influenza in the nonhuman primate model; dendritic cells and macrophages in simian immunodeficiency virus infection of nonhuman primates; pathogenesis of dengue and Zika virus infections in humans
Dr. Robbie B. Mailliard
Website SciProfiles
Guest Editor
University of Pittsburgh, Pittsburgh, PA 15261, USA
Interests: role of dendritic cells in the induction and regulation of innate and adaptive immunity; impact of pathogens on human dendritic cell phenotype and function; ex vivo generation and programming of human dendritic cells for the purpose of developing effective cellular based immunotherapies to treat chronic diseases including cancer and HIV

Special Issue Information

Dear Colleagues,

Dendritic cells are key mediators of innate immunity and play an integral role in inducing adaptive immune responses to viruses. Specialized subsets of dendritic cells serve diverse functions, from capturing antigen in peripheral tissues and migrating to lymph nodes where they engage antigen-specific T cells, to producing copious quantities of type-I interferon in response to virus infection. Dendritic cell-based immunotherapy for viral infections is beginning to show promise following the implementation of this strategy to treat cancer. However, dendritic cells are also targets of immune evasion strategies by viruses and can serve as Trojan horses to facilitate virus spread in the host. In this review, we explore the varied contributions of this critical immune cell to antiviral immunity.

Dr. Simon M. Barratt-Boyes
Dr. Robbie B. Mailliard
Guest Editors

Manuscript Submission Information

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Keywords

  • dendritic cell
  • virus immunity
  • therapeutic vaccination
  • immune evasion

Published Papers (8 papers)

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Editorial

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Open AccessEditorial
Dendritic Cells and Antiviral Defense
Viruses 2020, 12(10), 1152; https://doi.org/10.3390/v12101152 - 12 Oct 2020
Abstract
Dendritic cells (DCs) play a fundamental and central role in the immune response, acting as a critical link between the innate and adaptive branches of immunity [...] Full article
(This article belongs to the Special Issue Dendritic Cells and Antiviral Defense)

Research

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Open AccessArticle
Regulation of Transcription Factor E2-2 in Human Plasmacytoid Dendritic Cells by Monocyte-Derived TNFα
Viruses 2020, 12(2), 162; https://doi.org/10.3390/v12020162 - 31 Jan 2020
Cited by 1
Abstract
Plasmacytoid dendritic cells (pDCs) are innate immune cells and potent producers of interferon alpha (IFNα). Regulation of pDCs is crucial for prevention of aberrant IFN production. Transcription factor E2-2 (TCF4) regulates pDC development and function, but mechanisms of E2-2 control have not been [...] Read more.
Plasmacytoid dendritic cells (pDCs) are innate immune cells and potent producers of interferon alpha (IFNα). Regulation of pDCs is crucial for prevention of aberrant IFN production. Transcription factor E2-2 (TCF4) regulates pDC development and function, but mechanisms of E2-2 control have not been investigated. We used freshly-isolated human peripheral blood mononuclear cells stimulated with toll-like receptor 7, 9, and 4 agonists to determine which factors regulate E2-2. After activation, pDCs decreased E2-2 expression. E2-2 downregulation occurred during the upregulation of costimulatory markers, after maximal IFN production. In congruence with previous reports in mice, we found that primary human pDCs that maintained high E2-2 levels produced more IFN, and had less expression of costimulatory markers. Stimulation of purified pDCs did not lead to E2-2 downregulation; therefore, we investigated if cytokine signaling regulates E2-2 expression. We found that tumor necrosis factor alpha (TNFα) produced by monocytes caused decreased E2-2 expression. All together, we established that primary human pDCs decrease E2-2 in response to TNFα and E2-2 low pDCs produce less IFN but exhibit more costimulatory molecules. Altered expression of E2-2 may represent a mechanism to attenuate IFN production and increase activation of the adaptive immune compartment. Full article
(This article belongs to the Special Issue Dendritic Cells and Antiviral Defense)
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Open AccessArticle
Herpes Simplex Virus Type-2 Paralyzes the Function of Monocyte-Derived Dendritic Cells
Viruses 2020, 12(1), 112; https://doi.org/10.3390/v12010112 - 16 Jan 2020
Cited by 3
Abstract
Herpes simplex viruses not only infect a variety of different cell types, including dendritic cells (DCs), but also modulate important cellular functions in benefit of the virus. Given the relevance of directed immune cell migration during the initiation of potent antiviral immune responses, [...] Read more.
Herpes simplex viruses not only infect a variety of different cell types, including dendritic cells (DCs), but also modulate important cellular functions in benefit of the virus. Given the relevance of directed immune cell migration during the initiation of potent antiviral immune responses, interference with DC migration constitutes a sophisticated strategy to hamper antiviral immunity. Notably, recent reports revealed that HSV-1 significantly inhibits DC migration in vitro. Thus, we aimed to investigate whether HSV-2 also modulates distinct hallmarks of DC biology. Here, we demonstrate that HSV-2 negatively interferes with chemokine-dependent in vitro migration capacity of mature DCs (mDCs). Interestingly, rather than mediating the reduction of the cognate chemokine receptor expression early during infection, HSV-2 rapidly induces β2 integrin (LFA-1)-mediated mDC adhesion and thereby blocks mDC migration. Mechanistically, HSV-2 triggers the proteasomal degradation of the negative regulator of β2 integrin activity, CYTIP, which causes the constitutive activation of LFA-1 and thus mDC adhesion. In conclusion, our data extend and strengthen recent findings reporting the reduction of mDC migration in the context of a herpesviral infection. We thus hypothesize that hampering antigen delivery to secondary lymphoid organs by inhibition of mDC migration is an evolutionary conserved strategy among distinct members of Herpesviridae. Full article
(This article belongs to the Special Issue Dendritic Cells and Antiviral Defense)
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Review

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Open AccessReview
Contribution of Dendritic Cells in Protective Immunity against Respiratory Syncytial Virus Infection
Viruses 2020, 12(1), 102; https://doi.org/10.3390/v12010102 - 15 Jan 2020
Cited by 3
Abstract
Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in infants and the elderly. The socioeconomic burden of RSV infection is substantial because it leads to serious respiratory problems, subsequent hospitalization, and mortality. Despite its clinical significance, a safe and [...] Read more.
Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in infants and the elderly. The socioeconomic burden of RSV infection is substantial because it leads to serious respiratory problems, subsequent hospitalization, and mortality. Despite its clinical significance, a safe and effective vaccine is not yet available to prevent RSV infection. Upon RSV infection, lung dendritic cells (DCs) detecting pathogens migrate to the lymph nodes and activate the adaptive immune response. Therefore, RSV has evolved various immunomodulatory strategies to inhibit DC function. Due to the capacity of RSV to modulate defense mechanisms in hosts, RSV infection results in inappropriate activation of immune responses resulting in immunopathology and frequent reinfection throughout life. This review discusses how DCs recognize invading RSV and induce adaptive immune responses, as well as the regulatory mechanisms mediated by RSV to disrupt DC functions and ultimately avoid host defenses. Full article
(This article belongs to the Special Issue Dendritic Cells and Antiviral Defense)
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Open AccessReview
Role of Dendritic Cells in Exposing Latent HIV-1 for the Kill
Viruses 2020, 12(1), 37; https://doi.org/10.3390/v12010037 - 28 Dec 2019
Cited by 1
Abstract
The development of effective yet nontoxic strategies to target the latent human immunodeficiency virus-1 (HIV-1) reservoir in antiretroviral therapy (ART)-suppressed individuals poses a critical barrier to a functional cure. The ‘kick and kill’ approach to HIV eradication entails proviral reactivation during ART, coupled [...] Read more.
The development of effective yet nontoxic strategies to target the latent human immunodeficiency virus-1 (HIV-1) reservoir in antiretroviral therapy (ART)-suppressed individuals poses a critical barrier to a functional cure. The ‘kick and kill’ approach to HIV eradication entails proviral reactivation during ART, coupled with generation of cytotoxic T lymphocytes (CTLs) or other immune effectors equipped to eliminate exposed infected cells. Pharmacological latency reversal agents (LRAs) that have produced modest reductions in the latent reservoir ex vivo have not impacted levels of proviral DNA in HIV-infected individuals. An optimal cure strategy incorporates methods that facilitate sufficient antigen exposure on reactivated cells following the induction of proviral gene expression, as well as the elimination of infected targets by either polyfunctional HIV-specific CTLs or other immune-based strategies. Although conventional dendritic cells (DCs) have been used extensively for the purpose of inducing antigen-specific CTL responses in HIV-1 clinical trials, their immunotherapeutic potential as cellular LRAs has been largely ignored. In this review, we discuss the challenges associated with current HIV-1 eradication strategies, as well as the unharnessed potential of ex vivo-programmed DCs for both the ‘kick and kill’ of latent HIV-1. Full article
(This article belongs to the Special Issue Dendritic Cells and Antiviral Defense)
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Open AccessReview
Dendritic Cells in HIV/SIV Prophylactic and Therapeutic Vaccination
Viruses 2020, 12(1), 24; https://doi.org/10.3390/v12010024 - 24 Dec 2019
Cited by 1
Abstract
Dendritic cells (DCs) are involved in human and simian immunodeficiency virus (HIV and SIV) pathogenesis but also play a critical role in orchestrating innate and adaptive vaccine-specific immune responses. Effective HIV/SIV vaccines require strong antigen-specific CD4 T cell responses, cytotoxic activity of CD8 [...] Read more.
Dendritic cells (DCs) are involved in human and simian immunodeficiency virus (HIV and SIV) pathogenesis but also play a critical role in orchestrating innate and adaptive vaccine-specific immune responses. Effective HIV/SIV vaccines require strong antigen-specific CD4 T cell responses, cytotoxic activity of CD8 T cells, and neutralizing/non-neutralizing antibody production at mucosal and systemic sites. To develop a protective HIV/SIV vaccine, vaccine regimens including DCs themselves, protein, DNA, mRNA, virus vectors, and various combinations have been evaluated in different animal and human models. Recent studies have shown that DCs enhanced prophylactic HIV/SIV vaccine efficacy by producing pro-inflammatory cytokines, improving T cell responses, and recruiting effector cells to target tissues. DCs are also targets for therapeutic HIV/SIV vaccines due to their ability to reverse latency, present antigen, and augment T and B cell immunity. Here, we review the complex interactions of DCs over the course of HIV/SIV prophylactic and therapeutic immunizations, providing new insights into development of advanced DC-targeted HIV/SIV vaccines. Full article
(This article belongs to the Special Issue Dendritic Cells and Antiviral Defense)
Open AccessReview
When Dendritic Cells Go Viral: The Role of Siglec-1 in Host Defense and Dissemination of Enveloped Viruses
Viruses 2020, 12(1), 8; https://doi.org/10.3390/v12010008 - 19 Dec 2019
Cited by 3
Abstract
Dendritic cells (DCs) are among the first cells that recognize incoming viruses at the mucosal portals of entry. Initial interaction between DCs and viruses facilitates cell activation and migration to secondary lymphoid tissues, where these antigen presenting cells (APCs) prime specific adaptive immune [...] Read more.
Dendritic cells (DCs) are among the first cells that recognize incoming viruses at the mucosal portals of entry. Initial interaction between DCs and viruses facilitates cell activation and migration to secondary lymphoid tissues, where these antigen presenting cells (APCs) prime specific adaptive immune responses. Some viruses, however, have evolved strategies to subvert the migratory capacity of DCs as a way to disseminate infection systemically. Here we focus on the role of Siglec-1, a sialic acid-binding type I lectin receptor potently upregulated by type I interferons on DCs, that acts as a double edge sword, containing viral replication through the induction of antiviral immunity, but also favoring viral spread within tissues. Such is the case for distant enveloped viruses like human immunodeficiency virus (HIV)-1 or Ebola virus (EBOV), which incorporate sialic acid-containing gangliosides on their viral membrane and are effectively recognized by Siglec-1. Here we review how Siglec-1 is highly induced on the surface of human DCs upon viral infection, the way this impacts different antigen presentation pathways, and how enveloped viruses have evolved to exploit these APC functions as a potent dissemination strategy in different anatomical compartments. Full article
(This article belongs to the Special Issue Dendritic Cells and Antiviral Defense)
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Open AccessReview
The Role of Dendritic Cells in Immune Control and Vaccination against γ-Herpesviruses
Viruses 2019, 11(12), 1125; https://doi.org/10.3390/v11121125 - 05 Dec 2019
Cited by 3
Abstract
The two human oncogenic γ-herpesviruses, Epstein Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV), are prototypic pathogens that are controlled by T cell responses. Despite their ubiquitous distribution, persistent infections and transforming potential, most carriers’ immune systems control them for life. Therefore, they [...] Read more.
The two human oncogenic γ-herpesviruses, Epstein Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV), are prototypic pathogens that are controlled by T cell responses. Despite their ubiquitous distribution, persistent infections and transforming potential, most carriers’ immune systems control them for life. Therefore, they serve as paradigms of how near-perfect cell-mediated immune control can be initiated and maintained for decades. Interestingly, EBV especially quite efficiently avoids dendritic cell (DC) activation, and little evidence exists that these most potent antigen-presenting cells of the human body are involved in the priming of immune control against this tumor virus. However, DCs can be harnessed therapeutically to expand virus-specific T cells for adoptive transfer therapy of patients with virus-associated malignancies and are also currently explored for vaccinations. Unfortunately, despite 55 and 25 years of research on EBV and KSHV, respectively, the priming of their immune control that belongs to the most robust and durable immune responses in humans still remains unclear. Full article
(This article belongs to the Special Issue Dendritic Cells and Antiviral Defense)
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