Regulatory Effect of IFN-κ, A Novel Type I IFN, On Cytokine Production by Cells of the Innate Immune System

Little is known about the response of non-model invertebrates, such as oysters, to virus infection. The vertebrate innate immune system detects virus-derived nucleic acids to trigger the type I IFN pathway, leading to the transcription of hundreds of IFN-stimulated genes (ISGs) that exert antiviral functions. Invertebrates were thought to lack the IFN pathway based on the absence of IFN or ISGs encoded in model invertebrate genomes. However, the oyster genome encodes many ISGs, including the well-described antiviral protein viperin. In this study, we characterized oyster viperin and showed that it localizes to caveolin-1 and inhibits dengue virus replication in a heterologous model. In a second set of experiments, we have provided evidence that the haemolymph from poly(I : C)-injected oysters contains a heat-stable, protease-susceptible factor that induces haemocyte transcription of viperin mRNA in conjunction with upregulation of IFN regulatory factor. Collectively, these results support the concept that oysters have antiviral systems that are homologous to the vertebrate IFN pathway.

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The innate immune system in SLE: type I interferons and dendritic cells

Lupus ◽

10.1177/0961203308090020 ◽

2008 ◽

Vol 17 (5) ◽

pp. 394-399 ◽

Cited By ~ 200

Author(s):

L Rönnblom ◽

V Pascual

Keyword(s):

Dendritic Cells ◽

Immune System ◽

Innate Immune System ◽

Innate Immune ◽

Type I Interferons ◽

Type I

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The innate immune system in human systemic lupus erythematosus

Clinical Science ◽

10.1042/cs20160415 ◽

2017 ◽

Vol 131 (8) ◽

pp. 625-634 ◽

Cited By ~ 19

Author(s):

Marc Weidenbusch ◽

Onkar P. Kulkarni ◽

Hans-Joachim Anders

Keyword(s):

Systemic Lupus Erythematosus ◽

Immune System ◽

Lupus Erythematosus ◽

Innate Immune System ◽

Innate Immune ◽

Type I ◽

Human Systemic Lupus Erythematosus ◽

Systemic Lupus ◽

Adaptive Immune

Although the role of adaptive immune mechanisms, e.g. autoantibody formation and abnormal T-cell activation, has been long noted in the pathogenesis of human systemic lupus erythematosus (SLE), the role of innate immunity has been less well characterized. An intricate interplay between both innate and adaptive immune elements exists in protective anti-infective immunity as well as in detrimental autoimmunity. More recently, it has become clear that the innate immune system in this regard not only starts inflammation cascades in SLE leading to disease flares, but also continues to fuel adaptive immune responses throughout the course of the disease. This is why targeting the innate immune system offers an additional means of treating SLE. First trials assessing the efficacy of anti-type I interferon (IFN) therapy or modulators of pattern recognition receptor (PRR) signalling have been attempted. In this review, we summarize the available evidence on the role of several distinct innate immune elements, especially neutrophils and dendritic cells as well as the IFN system, as well as specific innate PRRs along with their signalling pathways. Finally, we highlight recent clinical trials in SLE addressing one or more of the aforementioned components of the innate immune system.

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Virus Caused Imbalance of Type I IFN Responses and Inflammation in COVID-19

Frontiers in Immunology ◽

10.3389/fimmu.2021.633769 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jintao Zhang ◽

Chunyuan Zhao ◽

Wei Zhao

Keyword(s):

Innate Immunity ◽

Innate Immune System ◽

Innate Immune ◽

Type I Interferons ◽

Type I ◽

Type I Ifn ◽

Antiviral Responses ◽

Public Health Challenges ◽

Host Innate Immunity ◽

Efficient Elimination

The global expansion of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as one of the greatest public health challenges and imposes a great threat to human health. Innate immunity plays vital roles in eliminating viruses through initiating type I interferons (IFNs)-dependent antiviral responses and inducing inflammation. Therefore, optimal activation of innate immunity and balanced type I IFN responses and inflammation are beneficial for efficient elimination of invading viruses. However, SARS-CoV-2 manipulates the host’s innate immune system by multiple mechanisms, leading to aberrant type I IFN responses and excessive inflammation. In this review, we will emphasize the recent advances in the understanding of the crosstalk between host innate immunity and SARS-CoV-2 to explain the imbalance between inflammation and type I IFN responses caused by viral infection, and explore potential therapeutic targets for COVID-19.

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Effects of Overexpression of the Egyptian Fruit Bat Innate Immune Genes on Filovirus Infections in the Host Cells

Frontiers in Virology ◽

10.3389/fviro.2021.759655 ◽

2021 ◽

Vol 1 ◽

Author(s):

Ivan V. Kuzmin ◽

Palaniappan Ramanathan ◽

Christopher F. Basler ◽

Alexander Bukreyev

Keyword(s):

Immune System ◽

Innate Immune System ◽

Innate Immune ◽

Host Cells ◽

Type I ◽

Fluorescent Reporter ◽

Immune Genes ◽

Fruit Bat ◽

Virus Clearance ◽

Innate Immune Genes

Bats constitute a large and diverse group of mammals with unique characteristics. One of these is the ability of bats to maintain various pathogens, particularly viruses, without evidence of disease. The innate immune system has been implicated as one of the important components involved in this process. However, in contrast to the human innate immune system, little data is available for bats. In the present study we generated 23 fusion constructs of innate immune genes of Egyptian fruit bat (Rousettus aegyptiacus) with mCherry as a fluorescent reporter. We evaluated the effects of overexpressing these genes on the replication of Marburg and Ebola viruses in the Egyptian fruit bat cell line R06EJ. Both viruses were substantially inhibited by overexpression of type I, II and III interferons, as well as by DDX58 (RIG-I), IFIH1, and IRF1. Our observations suggest that the broad antiviral activity of these genes reported previously in human cells is conserved in Egyptian fruit bats and these possess anti-filovirus activities that may contribute to the efficient virus clearance.

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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.

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Fundamental properties of the mammalian innate immune system revealed by multispecies comparison of type I interferon responses

PLoS Biology ◽

10.1371/journal.pbio.2004086 ◽

2017 ◽

Vol 15 (12) ◽

pp. e2004086 ◽

Cited By ~ 92

Author(s):

Andrew E. Shaw ◽

Joseph Hughes ◽

Quan Gu ◽

Abdelkader Behdenna ◽

Joshua B. Singer ◽

...

Keyword(s):

Immune System ◽

Innate Immune System ◽

Type I Interferon ◽

Innate Immune ◽

Type I ◽

Fundamental Properties ◽

Interferon Responses

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Eosinophilic Esophagitis and Microbiota: State of the Art

Frontiers in Immunology ◽

10.3389/fimmu.2021.595762 ◽

2021 ◽

Vol 12 ◽

Author(s):

Maurizio Mennini ◽

Renato Tambucci ◽

Carla Riccardi ◽

Francesca Rea ◽

Paola De Angelis ◽

...

Keyword(s):

Immune System ◽

Lamina Propria ◽

Eosinophilic Esophagitis ◽

Innate Immune System ◽

Plasma Cells ◽

Innate Immune ◽

Type I ◽

Potential Implication ◽

Food Antigens ◽

Normal Oesophagus

Eosinophilic esophagitis (EoE) is a chronic, food-triggered, immune-mediated disease of the oesophagus, clinically characterized by symptoms referred to oesophagal dysfunction, and histologically defined by an eosinophil productive inflammation of the oesophagal mucosa, among other cell types. The involvement of an adaptive Th2-type response to food antigens in EoE was known since 2000; several cytokines and chemokines promote food-specific responses, during which local production of IgE, but also IgG4 derived from plasma cells in lamina propria of oesophagal mucosa might play an important role. Evidence pointing towards a possible role for the innate immunity in EoE has arisen recently. Together, this evidence gives rise to a potential role that the innate immune system in general, and also the microbial pattern recognition receptors (PRRs) might play in EoE pathogenesis. Among PRRs, Toll-like receptors (TLRs) are type-I transmembrane receptors expressed both on epithelial and lamina propria cells with the capacity to distinguish between pathogen and commensal microbes. As TLRs in the different intestinal epithelia represent the primary mechanism of epithelial recognition of bacteria, this evidence underlines that oesophagal TLR-dependent signaling pathways in EoE support the potential implication of microbiota and the innate immune system in the pathogenesis of this disease. The oesophagal mucosa hosts a resident microbiota, although in a smaller population as compared with other districts of the gastrointestinal tract. Few studies have focused on the composition of the microbiota of the normal oesophagus alone. Still, additional information has come from studies investigating the oesophagal microbiota in disease and including healthy patients as controls. Our review aims to describe all the evidence on the oesophagal and intestinal microbiota in patients with EoE to identify the specific features of dysbiosis in this condition.

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Innate Immune Training with Bacterial Extracts Enhances Lung Macrophage Recruitment to Protect from Betacoronavirus Infection

Journal of Innate Immunity ◽

10.1159/000519699 ◽

2021 ◽

pp. 1-13

Author(s):

Manuel Salzmann ◽

Patrick Haider ◽

Christoph Kaun ◽

Mira Brekalo ◽

Boris Hartmann ◽

...

Keyword(s):

Immune System ◽

Rna Sequencing ◽

Lung Tissue ◽

Innate Immune System ◽

Intermediate Stage ◽

Innate Immune ◽

Type I ◽

Tissue Samples ◽

Beneficial Effects ◽

Lung Macrophages

Training of the innate immune system with orally ingested bacterial extracts was demonstrated to have beneficial effects on infection clearance and disease outcome. The aim of our study was to identify cellular and molecular processes responsible for these immunological benefits. We used a murine coronavirus (MCoV) A59 mouse model treated with the immune activating bacterial extract Broncho-Vaxom (BV) OM-85. Tissue samples were analysed with qPCR, RNA sequencing, histology, and flow cytometry. After BV OM-85 treatment, interstitial macrophages accumulated in lung tissue leading to a faster response of type I interferon (IFN) signalling after MCoV infection resulting in overall lung tissue protection. Moreover, RNA sequencing showed that lung tissue from mice receiving BV OM-85 resembled an intermediate stage between healthy and viral infected lung tissue at day 4, indicating a faster return to normal tissue homoeostasis. The pharmacologic effect was mimicked by adoptively transferring naive lung macrophages into lungs from recipient mice before virus infection. The beneficial effect of BV OM-85 was abolished when inhibiting initial type I IFN signalling. Overall, our data suggest that BV OM-85 enhances lung macrophages allowing for a faster IFN response towards a viral challenge as part of the oral-induced innate immune system training.

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A Sendai Virus-Derived RNA Agonist of RIG-I as a Virus Vaccine Adjuvant

Journal of Virology ◽

10.1128/jvi.02338-12 ◽

2012 ◽

Vol 87 (3) ◽

pp. 1290-1300 ◽

Cited By ~ 70

Author(s):

L. Martínez-Gil ◽

P. H. Goff ◽

R. Hai ◽

A. García-Sastre ◽

M. L. Shaw ◽

...

Keyword(s):

Immune System ◽

Innate Immune System ◽

Type I Interferon ◽

Sendai Virus ◽

Innate Immune ◽

Specific Response ◽

Type I ◽

Potent Inducer ◽

Starting Point

ABSTRACTThe innate immune system is responsible for recognizing invading pathogens and initiating a protective response. In particular, the retinoic acid-inducible gene 1 protein (RIG-I) participates in the recognition of single- and double-stranded RNA viruses. RIG-I activation leads to the production of an appropriate cytokine and chemokine cocktail that stimulates an antiviral state and drives the adaptive immune system toward an efficient and specific response against the ongoing infection. One of the best-characterized natural RIG-I agonists is the defective interfering (DI) RNA produced by Sendai virus strain Cantell. This 546-nucleotide RNA is a well-known activator of the innate immune system and an extremely potent inducer of type I interferon. We designed anin vitro-transcribed RNA that retains the type I interferon stimulatory properties, and the RIG-I affinity of the Sendai virus produced DI RNA bothin vitroandin vivo. Thisin vitro-synthesized RNA is capable of enhancing the production of anti-influenza virus hemagglutinin (HA)-specific IgG after intramuscular or intranasal coadministration with inactivated H1N1 2009 pandemic vaccine. Furthermore, our adjuvant is equally effective at increasing the efficiency of an influenza A/Puerto Rico/8/34 virus inactivated vaccine as a poly(I·C)- or a squalene-based adjuvant. Ourin vitro-transcribed DI RNA represents an excellent tool for the study of RIG-I agonists as vaccine adjuvants and a starting point in the development of such a vaccine.

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