Insect baculoviruses strongly potentiate adaptive immune responses by inducing type I IFN

Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by chronic inflammation of the salivary and lacrimal glands and extra-glandular lesions. Adaptive immune response including T- and B-cell activation contributes to the development of SS. However, its pathogenesis has not yet been elucidated. In addition, several patients with SS present with the type I interferon (IFN) signature, which is the upregulation of the IFN-stimulated genes induced by type I IFN. Thus, innate immune responses including type I IFN activity are associated with SS pathogenesis. Recent studies have revealed the presence of activation pattern recognition receptors (PRRs) including Toll-like receptors, RNA sensor retinoic acid-inducible gene I and melanoma differentiation-associated gene 5, and inflammasomes in infiltrating and epithelial cells of the salivary glands among patients with SS. In addition, the activation of PRRs via the downstream pathway such as the type I IFN signature and nuclear factor kappa B can directly cause organ inflammation, and it is correlated with the activation of adaptive immune responses. Therefore, this study assessed the role of the innate immune signal pathway in the development of inflammation and immune abnormalities in SS.

Download Full-text

The Molecular Interactions of ZIKV and DENV with the Type-I IFN Response

Vaccines ◽

10.3390/vaccines8030530 ◽

2020 ◽

Vol 8 (3) ◽

pp. 530

Author(s):

Rosa C. Coldbeck-Shackley ◽

Nicholas S. Eyre ◽

Michael R. Beard

Keyword(s):

Immune Responses ◽

Molecular Interactions ◽

Molecular Mechanisms ◽

Type I Interferon ◽

Control Measures ◽

Type I ◽

Type I Ifn ◽

Adaptive Immune ◽

Vaccination Strategies ◽

Significant Disease

Zika Virus (ZIKV) and Dengue Virus (DENV) are related viruses of the Flavivirus genus that cause significant disease in humans. Existing control measures have been ineffective at curbing the increasing global incidence of infection for both viruses and they are therefore prime targets for new vaccination strategies. Type-I interferon (IFN) responses are important in clearing viral infection and for generating efficient adaptive immune responses towards infection and vaccination. However, ZIKV and DENV have evolved multiple molecular mechanisms to evade type-I IFN production. This review covers the molecular interactions, from detection to evasion, of these viruses with the type-I IFN response. Additionally, we discuss how this knowledge can be exploited to improve the design of new vaccine strategies.

Download Full-text

STING: a master regulator in the cancer-immunity cycle

Molecular Cancer ◽

10.1186/s12943-019-1087-y ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 28

Author(s):

Yuanyuan Zhu ◽

Xiang An ◽

Xiao Zhang ◽

Yu Qiao ◽

Tongsen Zheng ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Immune Responses ◽

Type I Interferons ◽

Type I ◽

Type I Ifn ◽

Negative Effects ◽

Independent Manner ◽

Adaptive Immune ◽

Cancer Immunity

Abstract The aberrant appearance of DNA in the cytoplasm triggers the activation of cGAS-cGAMP-STING signaling and induces the production of type I interferons, which play critical roles in activating both innate and adaptive immune responses. Recently, numerous studies have shown that the activation of STING and the stimulation of type I IFN production are critical for the anticancer immune response. However, emerging evidence suggests that STING also regulates anticancer immunity in a type I IFN-independent manner. For instance, STING has been shown to induce cell death and facilitate the release of cancer cell antigens. Moreover, STING activation has been demonstrated to enhance cancer antigen presentation, contribute to the priming and activation of T cells, facilitate the trafficking and infiltration of T cells into tumors and promote the recognition and killing of cancer cells by T cells. In this review, we focus on STING and the cancer immune response, with particular attention to the roles of STING activation in the cancer-immunity cycle. Additionally, the negative effects of STING activation on the cancer immune response and non-immune roles of STING in cancer have also been discussed.

Download Full-text

Simian Immunodeficiency Virus Infection of Rhesus Macaques Results in Delayed Zika Virus Clearance

mBio ◽

10.1128/mbio.02790-19 ◽

2019 ◽

Vol 10 (6) ◽

Cited By ~ 3

Author(s):

Carol L. Vinton ◽

Samuel J. Magaziner ◽

Kimberly A. Dowd ◽

Shelly J. Robertson ◽

Emerito Amaro-Carambot ◽

...

Keyword(s):

Immune Responses ◽

Zika Virus ◽

Neutralizing Antibodies ◽

Rhesus Macaques ◽

Type I Interferons ◽

Type I ◽

Adaptive Immune Responses ◽

Zikv Infection ◽

Adaptive Immune ◽

Immunodeficiency Virus

ABSTRACT Flaviviruses are controlled by adaptive immune responses but are exquisitely sensitive to interferon-stimulated genes (ISGs). How coinfections, particularly simian immunodeficiency viruses (SIVs), that induce robust ISG signatures influence flavivirus clearance and pathogenesis is unclear. Here, we studied how Zika virus (ZIKV) infection is modulated in SIV-infected nonhuman primates. We measured ZIKV replication, cellular ZIKV RNA levels, and immune responses in non-SIV-infected and SIV-infected rhesus macaques (RMs), which we infected with ZIKV. Coinfected animals had a 1- to 2-day delay in peak ZIKV viremia, which was 30% of that in non-SIV-infected animals. However, ZIKV viremia was significantly prolonged in SIV-positive (SIV+) RMs. ISG levels at the time of ZIKV infection were predictive for lower ZIKV viremia in the SIV+ RMs, while prolonged ZIKV viremia was associated with muted and delayed adaptive responses in SIV+ RMs. IMPORTANCE Immunocompromised individuals often become symptomatic with infections which are normally fairly asymptomatic in healthy individuals. The particular mechanisms that underlie susceptibility to coinfections in human immunodeficiency virus (HIV)-infected individuals are multifaceted. ZIKV and other flaviviruses are sensitive to neutralizing antibodies, whose production can be limited in HIV-infected individuals but are also sensitive to type I interferons, which are expressed at high levels in HIV-infected individuals. Data in this study highlight how individual components of the innate and adaptive immune responses which become perturbed in HIV-infected individuals influence ZIKV infection.

Download Full-text

Overview. Type I interferons as primers, activators and inhibitors of innate and adaptive immune responses

Immunology and Cell Biology ◽

10.1038/icb.2012.15 ◽

2012 ◽

Vol 90 (5) ◽

pp. 471-473 ◽

Cited By ~ 15

Author(s):

Paul J Hertzog

Keyword(s):

Immune Responses ◽

Type I Interferons ◽

Type I ◽

Adaptive Immune Responses ◽

Adaptive Immune

Download Full-text

Type I Interferons Mediate the Innate Cytokine Response to Recombinant Fowlpox Virus but Not the Induction of Plasmacytoid Dendritic Cell-Dependent Adaptive Immunity

Journal of Virology ◽

10.1128/jvi.02618-09 ◽

2010 ◽

Vol 84 (13) ◽

pp. 6549-6563 ◽

Cited By ~ 7

Author(s):

Erin L. Lousberg ◽

Cara K. Fraser ◽

Michael G. Tovey ◽

Kerrilyn R. Diener ◽

John D. Hayball

Keyword(s):

Immune Responses ◽

Plasmacytoid Dendritic Cell ◽

Type I Interferons ◽

Interleukin 12 ◽

Type I ◽

Adaptive Immune Responses ◽

Fowlpox Virus ◽

Adaptive Immune ◽

Type I Ifns

ABSTRACT Type I interferons (IFNs) are considered to be important mediators of innate immunity due to their inherent antiviral activity, ability to drive the transcription of a number of genes involved in viral clearance, and their role in the initiation of innate and adaptive immune responses. Due to the central role of type I IFNs, we sought to determine their importance in the generation of immunity to a recombinant vaccine vector fowlpox virus (FPV). In analyzing the role of type I IFNs in immunity to FPV, we show that they are critical to the secretion of a number of innate and proinflammatory cytokines, including type I IFNs themselves as well as interleukin-12 (IL-12), tumor necrosis factor-alpha (TNF-α), IL-6, and IL-1β, and that deficiency leads to enhanced virus-mediated antigen expression. Interestingly, however, type I IFNs were not required for adaptive immune responses to recombinant FPV even though plasmacytoid dendritic cells (pDCs), the primary producers of type I IFNs, have been shown to be requisite for this to occur. Furthermore, we provide evidence that the importance of pDCs may lie in their ability to capture and present virally derived antigen to T cells rather than in their capacity as professional type I IFN-producing cells.

Download Full-text

Interferon-Mediated Immunopathological Events Are Associated with Atypical Innate and Adaptive Immune Responses in Patients with Severe Acute Respiratory Syndrome

Journal of Virology ◽

10.1128/jvi.00527-07 ◽

2007 ◽

Vol 81 (16) ◽

pp. 8692-8706 ◽

Cited By ~ 203

Author(s):

Mark J. Cameron ◽

Longsi Ran ◽

Luoling Xu ◽

Ali Danesh ◽

Jesus F. Bermejo-Martin ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Immune Responses ◽

Viral Infections ◽

Fatal Outcome ◽

Careful Examination ◽

Type I ◽

Immunoglobulin Gene ◽

Adaptive Immune Responses ◽

Immune Genes ◽

Adaptive Immune

ABSTRACT It is not understood how immune inflammation influences the pathogenesis of severe acute respiratory syndrome (SARS). One area of strong controversy is the role of interferon (IFN) responses in the natural history of SARS. The fact that the majority of SARS patients recover after relatively moderate illness suggests that the prevailing notion of deficient type I IFN-mediated immunity, with hypercytokinemia driving a poor clinical course, is oversimplified. We used proteomic and genomic technology to systematically analyze host innate and adaptive immune responses of 40 clinically well-described patients with SARS during discrete phases of illness from the onset of symptoms to discharge or a fatal outcome. A novel signature of high IFN-α, IFN-γ, and IFN-stimulated chemokine levels, plus robust antiviral IFN-stimulated gene (ISG) expression, accompanied early SARS sequelae. As acute illness progressed, SARS patients entered a crisis phase linked to oxygen saturation profiles. The majority of SARS patients resolved IFN responses at crisis and expressed adaptive immune genes. In contrast, patients with poor outcomes showed deviated ISG and immunoglobulin gene expression levels, persistent chemokine levels, and deficient anti-SARS spike antibody production. We contend that unregulated IFN responses during acute-phase SARS may culminate in a malfunction of the switch from innate immunity to adaptive immunity. The potential for the use of the gene signatures we describe in this study to better assess the immunopathology and clinical management of severe viral infections, such as SARS and avian influenza (H5N1), is therefore worth careful examination.

Download Full-text

Tweaking Innate Immunity: The Promise of Innate Immunologicals as Anti-Infectives

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2006/195957 ◽

2006 ◽

Vol 17 (5) ◽

pp. 307-314 ◽

Cited By ~ 8

Author(s):

Kenneth L Rosenthal

Keyword(s):

Innate Immunity ◽

Immune System ◽

Immune Responses ◽

Innate Immune System ◽

Immune Defense ◽

Innate Immune ◽

Parasitic Infections ◽

Type I ◽

Adaptive Immune Responses ◽

Adaptive Immune

New and exciting insights into the importance of the innate immune system are revolutionizing our understanding of immune defense against infections, pathogenesis, and the treatment and prevention of infectious diseases. The innate immune system uses multiple families of germline-encoded pattern recognition receptors (PRRs) to detect infection and trigger a variety of antimicrobial defense mechanisms. PRRs are evolutionarily highly conserved and serve to detect infection by recognizing pathogen-associated molecular patterns that are unique to microorganisms and essential for their survival. Toll-like receptors (TLRs) are transmembrane signalling receptors that activate gene expression programs that result in the production of proinflammatory cytokines and chemokines, type I interferons and antimicrobial factors. Furthermore, TLR activation facilitates and guides activation of adaptive immune responses through the activation of dendritic cells. TLRs are localized on the cell surface and in endosomal/lysosomal compartments, where they detect bacterial and viral infections. In contrast, nucleotide-binding oligomerization domain proteins and RNA helicases are located in the cell cytoplasm, where they serve as intracellular PRRs to detect cytoplasmic infections, particularly viruses. Due to their ability to enhance innate immune responses, novel strategies to use ligands, synthetic agonists or antagonists of PRRs (also known as 'innate immunologicals') can be used as stand-alone agents to provide immediate protection or treatment against bacterial, viral or parasitic infections. Furthermore, the newly appreciated importance of innate immunity in initiating and shaping adaptive immune responses is contributing to our understanding of vaccine adjuvants and promises to lead to improved next-generation vaccines.

Download Full-text