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 Type I interferon responses to ischemic injury begin in the bone marrow of mice and humans and depend on Tet2, Nrf2, and Irf3

2019 ◽  
Author(s):  
David M. Calcagno ◽  
Richard P. Ng ◽  
Avinash Toomu ◽  
Claire Zhang ◽  
Kenneth Huang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Type I Interferon ◽  
Tissue Injury ◽  
Type I ◽  
Blood Neutrophils ◽  
Clinical Biomarker ◽  
Acute Mi ◽  
Molecular Patterns ◽  
Interferon Responses ◽  
Myeloid Progenitors

AbstractSterile tissue injury locally activates innate immune responses via interactions with damage associated molecular patterns (DAMPs). Here, by analyzing ∼120K single cell transcriptomes after myocardial infarction (MI) in mice and humans, we show neutrophil and monocyte subsets induce type I interferon (IFN) stimulated genes (ISGs) in myeloid progenitors of the bone marrow, far from the site of injury. In patients with acute MI, peripheral blood neutrophils and monocytes express ISGs at levels far beyond healthy individuals and comparable to patients with lupus. In the bone marrow of Tet2-/- mice, ISGs are spontaneously induced in myeloid progenitors and their progeny. In the heart, IFN responses are negatively regulated by Ccr2- resident macrophages in a Nrf2-dependent fashion. Our results show post-MI IFN signaling begins in the bone marrow, implicate multiple transcription factors in its regulation (Tet2, Irf3, Nrf2), and provide a clinical biomarker (ISG score) for studying post-MI IFN signaling in patients.

scholarly journals Synthetic rewiring and boosting type I interferon responses for visualization and counteracting viral infections

2020 ◽  
Vol 48 (20) ◽  
pp. 11799-11811
Author(s):  
Natascha Gödecke ◽  
Jan Riedel ◽  
Sabrina Herrmann ◽  
Sara Behme ◽  
Ulfert Rand ◽  
...  
Keyword(s):  
Positive Feedback ◽  
Viral Infections ◽  
Type I Interferon ◽  
Type I ◽  
First Line ◽  
Initial Stimulus ◽  
Sensor Actuator ◽  
Actuator System ◽  
Interferon Responses ◽  
Robust Sensing

Abstract Mammalian first line of defense against viruses is accomplished by the interferon (IFN) system. Viruses have evolved numerous mechanisms to reduce the IFN action allowing them to invade the host and/or to establish latency. We generated an IFN responsive intracellular hub by integrating the synthetic transactivator tTA into the chromosomal Mx2 locus for IFN-based activation of tTA dependent expression modules. The additional implementation of a synthetic amplifier module with positive feedback even allowed for monitoring and reacting to infections of viruses that can antagonize the IFN system. Low and transient IFN amounts are sufficient to trigger these amplifier cells. This gives rise to higher and sustained—but optionally de-activatable—expression even when the initial stimulus has faded out. Amplification of the IFN response induced by IFN suppressing viruses is sufficient to protect cells from infection. Together, this interfaced sensor/actuator system provides a toolbox for robust sensing and counteracting viral infections.

scholarly journals STAT2 Knockout Syrian Hamsters Support Enhanced Replication and Pathogenicity of Human Adenovirus, Revealing an Important Role of Type I Interferon Response in Viral Control

2015 ◽  
Vol 11 (8) ◽  
pp. e1005084 ◽  
Author(s):  
Karoly Toth ◽  
Sang R. Lee ◽  
Baoling Ying ◽  
Jacqueline F. Spencer ◽  
Ann E. Tollefson ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Human Adenovirus ◽  
Interferon Response ◽  
Type I ◽  
Viral Control ◽  
Syrian Hamsters

Role of Leptin and SOCS3 in Inhibiting the Type I Interferon Response During Obesity

Inflammation ◽  
2016 ◽  
Vol 40 (1) ◽  
pp. 58-67 ◽  
Author(s):  
Elí Terán-Cabanillas ◽  
Jesús Hernández
Keyword(s):  
Type I Interferon ◽  
Interferon Response ◽  
Type I

scholarly journals Sex-Dependent Intestinal Replication of an Enteric Virus

2017 ◽  
Vol 91 (7) ◽  
Author(s):  
Christopher M. Robinson ◽  
Yao Wang ◽  
Julie K. Pfeiffer
Keyword(s):  
Gastrointestinal Tract ◽  
Viral Replication ◽  
Sex Hormones ◽  
Viral Infections ◽  
Type I Interferon ◽  
Enteric Virus ◽  
Interferon Response ◽  
Sex Bias ◽  
Type I ◽  
Peripheral Tissues

ABSTRACT Coxsackievirus is an enteric virus that initiates infection in the gastrointestinal tract before disseminating to peripheral tissues to cause disease, but intestinal factors that influence viral replication are understudied. Furthermore, a sex bias for severe sequelae from coxsackievirus infections has been observed in humans. While mouse models mimicking human pathogenesis have been well characterized, many of these experiments use intraperitoneal injection of coxsackievirus to infect mice, bypassing the intestine. In light of recent studies identifying intestinal factors, such as the microbiota, that alter enteric viral replication, we sought to investigate coxsackievirus replication within the intestine. Here, we orally infected mice with coxsackievirus B3 (CVB3) and found that CVB3 replication in the intestine is sex dependent. CVB3 replicated efficiently in the intestine of male mice but not female mice. Additionally, we found that the type I interferon response and sex hormones can alter both viral replication and lethality. Overall, these data suggest that sex and the immune response play a vital role in CVB3 replication in the intestine and should be considered in light of the sex bias observed in human disease. IMPORTANCE Sex bias in severe sequelae from enteric viral infections has been observed. Since viruses have evolved to achieve optimal levels of fitness in their environmental niches, it is imperative to study viruses at the site of initial replication. Here, we used an oral inoculation system for CVB3, which follows the natural route of infection in the gastrointestinal tract. We found that sex can influence the replication of CVB3 in the intestine. Additionally, the type I interferon response and sex hormones alter both CVB3 intestinal replication and lethality. Overall this work highlights the fact that sex should be considered in investigations of enteric viral replication and pathogenesis.

scholarly journals Defining the Role of Type I Interferon Signaling in the Increased Accumulation of Versican in Lungs of Mice Exposed to Influenza Infection

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Jourdan Brune ◽  
Mary Chang ◽  
Jessica Felgenhauer ◽  
Brian Johnson ◽  
Megan Larmore ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Influenza Infection ◽  
Type I ◽  
Interferon Signaling

scholarly journals NSUN2-mediated m5C methylation of IRF3 mRNA negatively regulates type I interferon responses

2021 ◽  
Author(s):  
Hongyun Wang ◽  
Lu Zhang ◽  
Cong Zeng ◽  
Jiangpeng Feng ◽  
Yu Zhou ◽  
...  
Keyword(s):  
Viral Infection ◽  
Type I Interferon ◽  
Sendai Virus ◽  
Negative Regulator ◽  
Interferon Response ◽  
Rna Modification ◽  
Type I ◽  
Mrna Levels ◽  
Interferon Responses

5-Methylcytosine (m5C) is a widespread post-transcriptional RNA modification and is reported to be involved in manifold cellular responses and biological processes through regulating RNA metabolism. However, its regulatory role in antiviral innate immunity has not yet been elucidated. Here, we report that NSUN2, a typical m5C methyltransferase, can negatively regulate type I interferon responses during viral infection. NSUN2 specifically mediates m5C methylation of IRF3 mRNA and accelerates its degradation, resulting in low levels of IRF3 and downstream IFN-β production. Knockout or knockdown of NSUN2 could enhance type I interferon responses and downstream ISG expression after viral infection in vitro. And in vivo, the antiviral innate responses is more dramatically enhanced in Nsun2+/− mice than in Nsun2+/+ mice. Four highly m5C methylated cytosines in IRF3 mRNA were identified, and their mutation could enhance the cellular IRF3 mRNA levels. Moreover, infection with Sendai virus (SeV), vesicular stomatitis virus (VSV), herpes simplex virus 1 (HSV-1), Zika virus (ZIKV), or especially SARS-CoV-2 resulted in a reduction in endogenous levels of NSUN2. Together, our findings reveal that NSUN2 serves as a negative regulator of interferon response by accelerating the fast turnover of IRF3 mRNA, while endogenous NSUN2 levels decrease after viral infection to boost antiviral responses for the effective elimination of viruses. Our results suggest a paradigm of innate antiviral immune responses ingeniously involving NSUN2-mediated m5C modification.

scholarly journals Mouse Model of SARS-CoV-2 Reveals Inflammatory Role of Type I Interferon Signaling

2020 ◽  
Author(s):  
Benjamin Goldman-Israelow ◽  
Eric Song ◽  
Tianyang Mao ◽  
Peiwen Lu ◽  
Amit Meir ◽  
...  
Keyword(s):  
Mouse Model ◽  
Type I Interferon ◽  
Type I ◽  
Interferon Signaling

scholarly journals Role of the Intracellular Domain of the Human Type I Interferon Receptor 2 Chain (IFNAR2c) in Interferon Signaling

2000 ◽  
Vol 275 (31) ◽  
pp. 23981-23985 ◽  
Author(s):  
Dean Russell-Harde ◽  
T. Charis Wagner ◽  
M. R. Sandhya Rani ◽  
David Vogel ◽  
Oscar Colamonici ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Type I ◽  
Interferon Signaling ◽  
Intracellular Domain ◽  
Human Type ◽  
Interferon Receptor

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. 

Sign in / Sign up

Export Citation Format

Share Document