scholarly journals IFN Signaling in Inflammation and Viral Infections: New Insights from Fish Models

Viruses ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 302 ◽  
Author(s):  
Christelle Langevin ◽  
Pierre Boudinot ◽  
Bertrand Collet
Keyword(s):  
Genome Duplication ◽  
Viral Infections ◽  
Type I Interferon ◽  
Type I ◽  
Adaptive Responses ◽  
Adjuvant Effect ◽  
Hematopoietic Stem ◽  
Fish Evolution ◽  
Duplication Events

The overarching structure of the type I interferon (IFN) system is conserved across vertebrates. However, the variable numbers of whole genome duplication events during fish evolution offer opportunities for the expansion, diversification, and new functionalization of the genes that are involved in antiviral immunity. In this review, we examine how fish models provide new insights about the implication of virus-driven inflammation in immunity and hematopoiesis. Mechanisms that have been discovered in fish, such as the strong adjuvant effect of type I IFN that is used with DNA vaccination, constitute good models to understand how virus-induced inflammatory mechanisms can interfere with adaptive responses. We also comment on new discoveries regarding the role of pathogen-induced inflammation in the development and guidance of hematopoietic stem cells in zebrafish. These findings raise issues about the potential interferences of viral infections with the establishment of the immune system. Finally, the recent development of genome editing provides new opportunities to dissect the roles of the key players involved in the antiviral response in fish, hence enhancing the power of comparative approaches.

scholarly journals Mechanisms of type I interferon action and its role in infections and diseases transmission in mammals

2017 ◽  
Vol 64 (2) ◽  
Author(s):  
Weronika Ratajczak ◽  
Paulina Niedźwiedzka-Rystwej ◽  
Beata Tokarz-Deptuła ◽  
Wiesław Deptuła
Keyword(s):  
Signaling Pathways ◽  
Crucial Role ◽  
Viral Infections ◽  
Type I Interferon ◽  
Type I Interferons ◽  
Type I ◽  
Interferon Stimulated Genes

Interferons (IFN) are pivotal regulators of immunological processes. The paper describes mainly type I interferons -α and –β and its recently recounted signaling pathways, especially ISG – interferon stimulated genes, having a crucial role in regulating IFN recruitment. Moreover, the paper shows the data on the role of interferons -α and –β in infections – not only commonly known viral infections, but also bacterial, fungal and parasitic. 

scholarly journals FOSL1 Inhibits Type I Interferon Responses to Malaria and Viral Infections by Blocking TBK1 and TRAF3/TRIF Interactions

mBio ◽  
2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Baowei Cai ◽  
Jian Wu ◽  
Xiao Yu ◽  
Xin-zhuan Su ◽  
Rong-Fu Wang
Keyword(s):  
Immune Responses ◽  
Drug Target ◽  
Malaria Parasite ◽  
Viral Infections ◽  
Type I Interferon ◽  
Innate Immune ◽  
Type I ◽  
Potential Drug Target ◽  
Chimeric Mice

ABSTRACT Innate immune response plays a critical role in controlling invading pathogens, but such an immune response must be tightly regulated. Insufficient or overactivated immune responses may lead to harmful or even fatal consequences. To dissect the complex host-parasite interactions and the molecular mechanisms underlying innate immune responses to infections, here we investigate the role of FOS-like antigen 1 (FOSL1) in regulating the host type I interferon (IFN-I) response to malaria parasite and viral infections. FOSL1 is known as a component of a transcription factor but was recently implicated in regulating the IFN-I response to malaria parasite infection. Here we show that FOSL1 can act as a negative regulator of IFN-I signaling. Upon stimulation with poly(I:C), malaria parasite-infected red blood cells (iRBCs), or vesicular stomatitis virus (VSV), FOSL1 “translocated” from the nucleus to the cytoplasm, where it inhibited the interactions between TNF receptor-associated factor 3 (TRAF3), TIR domain-containing adapter inducing IFN-β (TRIF), and Tank-binding kinase 1 (TBK1) via impairing K63-linked polyubiquitination of TRAF3 and TRIF. Importantly, FOSL1 knockout chimeric mice had lower levels of malaria parasitemia or VSV titers in peripheral blood and decreased mortality compared with wild-type (WT) mice. Thus, our findings have identified a new role for FOSL1 in negatively regulating the host IFN-I response to malaria and viral infections and have identified a potential drug target for controlling malaria and other diseases. IMPORTANCE Infections of pathogens can trigger vigorous host immune responses, including activation and production of type I interferon (IFN-I). In this study, we investigated the role of FOSL1, a molecule previously known as a transcription factor, in negatively regulating IFN-I responses to malaria and viral infections. We showed that FOSL1 was upregulated and translocated into the cytoplasm of cells after stimulation for IFN-I production. FOSL1 could affect TRAF3 and TRIF ubiquitination and consequently impaired the association of TRAF3, TRIF, and TBK1, leading to inhibition of IFN-I signaling. In vivo experiments with FOSL1 knockout chimeric mice further validated the negative role of FOSL1 in IFN-I production and antimicrobial responses. This report reveals a new functional role for FOSL1 in IFN-I signaling and dissects the mechanism by which FOSL1 regulates IFN-I responses to malaria and viral infections, which can be explored as a potential drug target for disease control and management.

scholarly journals Role of NLRs in the Regulation of Type I Interferon Signaling, Host Defense and Tolerance to Inflammation

2021 ◽  
Vol 22 (3) ◽  
pp. 1301
Author(s):  
Ioannis Kienes ◽  
Tanja Weidl ◽  
Nora Mirza ◽  
Mathias Chamaillard ◽  
Thomas A. Kufer
Keyword(s):  
Viral Infections ◽  
Type I Interferon ◽  
Tissue Injury ◽  
Interferon Response ◽  
Type I ◽  
Interferon Signaling ◽  
Microbial Products ◽  
Interferon Responses

Type I interferon signaling contributes to the development of innate and adaptive immune responses to either viruses, fungi, or bacteria. However, amplitude and timing of the interferon response is of utmost importance for preventing an underwhelming outcome, or tissue damage. While several pathogens evolved strategies for disturbing the quality of interferon signaling, there is growing evidence that this pathway can be regulated by several members of the Nod-like receptor (NLR) family, although the precise mechanism for most of these remains elusive. NLRs consist of a family of about 20 proteins in mammals, which are capable of sensing microbial products as well as endogenous signals related to tissue injury. Here we provide an overview of our current understanding of the function of those NLRs in type I interferon responses with a focus on viral infections. We discuss how NLR-mediated type I interferon regulation can influence the development of auto-immunity and the immune response to infection.

scholarly journals Host genetic susceptibility to viral infections: the role of type I interferon induction

2020 ◽  
Vol 21 (6-8) ◽  
pp. 365-379
Author(s):  
Marie Bourdon ◽  
Caroline Manet ◽  
Xavier Montagutelli
Keyword(s):  
Genetic Susceptibility ◽  
Viral Infections ◽  
Type I Interferon ◽  
Type I ◽  
Interferon Induction ◽  
Host Genetic

scholarly journals Type I interferon: friend or foe?

2010 ◽  
Vol 207 (10) ◽  
pp. 2053-2063 ◽  
Author(s):  
Giorgio Trinchieri
Keyword(s):  
Bacterial Infections ◽  
Viral Infections ◽  
Type I Interferon ◽  
Type I

Although the role of type I interferon (IFN) in the protection against viral infections has been known and studied for decades, its role in other immunologically relevant scenarios, including bacterial infections, shock, autoimmunity, and cancer, is less well defined and potentially much more complicated.

scholarly journals The Abstruse Side of Type I Interferon Immunotherapy for COVID-19 Cases with Comorbidities

2021 ◽  
Vol 1 (1) ◽  
pp. 49-59
Author(s):  
Selvakumar Subbian
Keyword(s):  
Infectious Diseases ◽  
Disease Severity ◽  
Type I Interferon ◽  
Host Factors ◽  
Type I ◽  
The Novel ◽  
Inflammatory Drugs ◽  
Precautionary Measures ◽  
Inducible Genes

The Coronavirus Disease-2019 (COVID-19) pandemic, caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has claimed 1.2 million people globally since December 2019. Although the host factors underpinning COVID-19 pathology are not fully understood, type I interferon (IFN-I) response is considered crucial for SARS-CoV-2 pathogenesis. Perturbations in IFN-I signaling and associated interferon-inducible genes (ISG) are among the primary disease severity indicators in COVID-19. Consequently, IFN-I therapy, either alone or in- combination with existing antiviral or anti-inflammatory drugs, is tested in many ongoing clinical trials to reduce COVID-19 mortality. Since signaling by the IFN-I family of molecules regulates host immune response to other infectious and non-infectious diseases, any imbalance in this family of cytokines would impact the clinical outcome of COVID-19, as well as other co-existing diseases. Therefore, it is imperative to evaluate the beneficial-versus-detrimental effects of IFN-I immunotherapy for COVID-19 patients with divergent disease severity and other co-existing conditions. This review article summarizes the role of IFN-I signaling in infectious and non-infectious diseases of humans. It highlights the precautionary measures to be considered before administering IFN-I to COVID-19 patients having other co-existing disorders. Finally, suggestions are proposed to improve IFN-I immunotherapy to COVID-19.

scholarly journals The Role of Optineurin in Antiviral Type I Interferon Production

2018 ◽  
Vol 9 ◽  
Author(s):  
Ahmed Outlioua ◽  
Marie Pourcelot ◽  
Damien Arnoult
Keyword(s):  
Type I Interferon ◽  
Type I ◽  
Interferon Production

scholarly journals Transcriptional role of p53 in interferon-mediated antiviral immunity

2008 ◽  
Vol 205 (8) ◽  
pp. 1929-1938 ◽  
Author(s):  
César Muñoz-Fontela ◽  
Salvador Macip ◽  
Luis Martínez-Sobrido ◽  
Lauren Brown ◽  
Joseph Ashour ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Viral Replication ◽  
Viral Infections ◽  
Suppressor Gene ◽  
Central Component ◽  
Type I ◽  
Infected Cells

Tumor suppressor p53 is activated by several stimuli, including DNA damage and oncogenic stress. Previous studies (Takaoka, A., S. Hayakawa, H. Yanai, D. Stoiber, H. Negishi, H. Kikuchi, S. Sasaki, K. Imai, T. Shibue, K. Honda, and T. Taniguchi. 2003. Nature. 424:516–523) have shown that p53 is also induced in response to viral infections as a downstream transcriptional target of type I interferon (IFN) signaling. Moreover, many viruses, including SV40, human papillomavirus, Kaposi's sarcoma herpesvirus, adenoviruses, and even RNA viruses such as polioviruses, have evolved mechanisms designated to abrogate p53 responses. We describe a novel p53 function in the activation of the IFN pathway. We observed that infected mouse and human cells with functional p53 exhibited markedly decreased viral replication early after infection. This early inhibition of viral replication was mediated both in vitro and in vivo by a p53-dependent enhancement of IFN signaling, specifically the induction of genes containing IFN-stimulated response elements. Of note, p53 also contributed to an increase in IFN release from infected cells. We established that this p53-dependent enhancement of IFN signaling is dependent to a great extent on the ability of p53 to activate the transcription of IFN regulatory factor 9, a central component of the IFN-stimulated gene factor 3 complex. Our results demonstrate that p53 contributes to innate immunity by enhancing IFN-dependent antiviral activity independent of its functions as a proapoptotic and tumor suppressor gene.

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