scholarly journals TBK1, a central kinase in innate immune sensing of nucleic acids and beyond

2020 ◽  
Vol 52 (7) ◽  
pp. 757-767 ◽  
Author(s):  
Ruyuan Zhou ◽  
Qian Zhang ◽  
Pinglong Xu
Keyword(s):  
Nucleic Acids ◽  
Cell Biology ◽  
Innate Immune ◽  
Type I ◽  
Interferon Stimulated Genes ◽  
Immune Sensing ◽  
Mitochondrial Antiviral Signaling ◽  
I Kappa B Kinase ◽  
Innate Immune Sensing ◽  
Mitochondrial Antiviral Signaling Protein

Abstract Sensing of intracellular and extracellular environments is one of the fundamental processes of cell. Surveillance of aberrant nucleic acids, derived either from invading pathogens or damaged organelle, is conducted by pattern recognition receptors (PRRs) including RIG-I-like receptors, cyclic GMP-AMP synthase, absent in melanoma 2, and a few members of toll-like receptors. TANK-binding kinase 1 (TBK1), along with its close analogue I-kappa-B kinase epsilon, is a central kinase in innate adaptor complexes linking activation of PRRs to mobilization of transcriptional factors that transcribe proinflammatory cytokines, type I interferon (IFN-α/β), and myriads interferon stimulated genes. However, it still remains elusive for the precise mechanisms of activation and execution of TBK1 in signaling platforms formed by innate adaptors mitochondrial antiviral signaling protein (MAVS), stimulator of interferon genes protein (STING), and TIR-domain-containing adapter-inducing interferon-β (TRIF), as well as its complex regulations. An atlas of TBK1 substrates is in constant expanding, setting TBK1 as a key node of signaling network and a dominant player in contexts of cell biology, animal models, and human diseases. Here, we review recent advancements of activation, regulations, and functions of TBK1 under these physiological and pathological contexts.

scholarly journals MAVS: A Two-Sided CARD Mediating Antiviral Innate Immune Signaling and Regulating Immune Homeostasis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yunqiang Chen ◽  
Yuheng Shi ◽  
Jing Wu ◽  
Nan Qi
Keyword(s):  
Signal Transduction ◽  
Innate Immune ◽  
Immune Homeostasis ◽  
Type I ◽  
Interferon Signaling ◽  
Immune Signaling ◽  
Post Translational Modifications ◽  
Innate Immune Signaling ◽  
Mitochondrial Antiviral Signaling ◽  
Mitochondrial Antiviral Signaling Protein

Mitochondrial antiviral signaling protein (MAVS) functions as a “switch” in the immune signal transduction against most RNA viruses. Upon viral infection, MAVS forms prion-like aggregates by receiving the cytosolic RNA sensor retinoic acid-inducible gene I-activated signaling and further activates/switches on the type I interferon signaling. While under resting state, MAVS is prevented from spontaneously aggregating to switch off the signal transduction and maintain immune homeostasis. Due to the dual role in antiviral signal transduction and immune homeostasis, MAVS has emerged as the central regulation target by both viruses and hosts. Recently, researchers show increasing interest in viral evasion strategies and immune homeostasis regulations targeting MAVS, especially focusing on the post-translational modifications of MAVS, such as ubiquitination and phosphorylation. This review summarizes the regulations of MAVS in antiviral innate immune signaling transduction and immune homeostasis maintenance.

scholarly journals Innate immune sensing of nucleic acids from mycobacteria

2014 ◽  
Vol 16 (12) ◽  
pp. 991-997 ◽  
Author(s):  
Lívia Harumi Yamashiro ◽  
Sérgio Costa Oliveira ◽  
André Báfica
Keyword(s):  
Nucleic Acids ◽  
Innate Immune ◽  
Immune Sensing ◽  
Innate Immune Sensing

Innate immune sensing of cancer: clues from an identified role for type I IFNs

2012 ◽  
Vol 61 (8) ◽  
pp. 1343-1347 ◽  
Author(s):  
Thomas F. Gajewski ◽  
Mercedes B. Fuertes ◽  
Seng-Ryong Woo
Keyword(s):  
Innate Immune ◽  
Type I ◽  
Type I Ifns ◽  
Immune Sensing ◽  
Innate Immune Sensing

scholarly journals RNase H2 catalytic core Aicardi-Goutières syndrome–related mutant invokes cGAS–STING innate immune-sensing pathway in mice

2016 ◽  
Vol 213 (3) ◽  
pp. 329-336 ◽  
Author(s):  
Vladislav Pokatayev ◽  
Naushaba Hasin ◽  
Hyongi Chon ◽  
Susana M. Cerritelli ◽  
Kiran Sakhuja ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Ventral Surface ◽  
Type I ◽  
Catalytic Core ◽  
Interferon Stimulated Genes ◽  
Early Embryonic Lethality ◽  
Genes Encoding ◽  
Immune Sensing ◽  
Rnase H2 ◽  
Innate Immune Sensing

The neuroinflammatory autoimmune disease Aicardi-Goutières syndrome (AGS) develops from mutations in genes encoding several nucleotide-processing proteins, including RNase H2. Defective RNase H2 may induce accumulation of self-nucleic acid species that trigger chronic type I interferon and inflammatory responses, leading to AGS pathology. We created a knock-in mouse model with an RNase H2 AGS mutation in a highly conserved residue of the catalytic subunit, Rnaseh2aG37S/G37S (G37S), to understand disease pathology. G37S homozygotes are perinatal lethal, in contrast to the early embryonic lethality previously reported for Rnaseh2b- or Rnaseh2c-null mice. Importantly, we found that the G37S mutation led to increased expression of interferon-stimulated genes dependent on the cGAS–STING signaling pathway. Ablation of STING in the G37S mice results in partial rescue of the perinatal lethality, with viable mice exhibiting white spotting on their ventral surface. We believe that the G37S knock-in mouse provides an excellent animal model for studying RNASEH2-associated autoimmune diseases.

scholarly journals Innate Immune Sensing of Viruses and Its Consequences for the Central Nervous System

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 170
Author(s):  
Hina Singh ◽  
Jeffrey Koury ◽  
Marcus Kaul
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Nerve Fibers ◽  
Innate Immune ◽  
Health Concern ◽  
Type I ◽  
Lectin Receptors ◽  
The Central Nervous System ◽  
Immune Sensing ◽  
Innate Immune Sensing

Viral infections remain a global public health concern and cause a severe societal and economic burden. At the organismal level, the innate immune system is essential for the detection of viruses and constitutes the first line of defense. Viral components are sensed by host pattern recognition receptors (PRRs). PRRs can be further classified based on their localization into Toll-like receptors (TLRs), C-type lectin receptors (CLR), retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), NOD-like receptors (NLRs) and cytosolic DNA sensors (CDS). TLR and RLR signaling results in production of type I interferons (IFNα and -β) and pro-inflammatory cytokines in a cell-specific manner, whereas NLR signaling leads to the production of interleukin-1 family proteins. On the other hand, CLRs are capable of sensing glycans present in viral pathogens, which can induce phagocytic, endocytic, antimicrobial, and pro- inflammatory responses. Peripheral immune sensing of viruses and the ensuing cytokine response can significantly affect the central nervous system (CNS). But viruses can also directly enter the CNS via a multitude of routes, such as the nasal epithelium, along nerve fibers connecting to the periphery and as cargo of infiltrating infected cells passing through the blood brain barrier, triggering innate immune sensing and cytokine responses directly in the CNS. Here, we review mechanisms of viral immune sensing and currently recognized consequences for the CNS of innate immune responses to viruses.

scholarly journals Murine Leukemia Virus Exploits Innate Sensing by Toll-Like Receptor 7 in B-1 Cells To Establish Infection and Locally Spread in Mice

2019 ◽  
Vol 93 (21) ◽  
Author(s):  
Ruoxi Pi ◽  
Akiko Iwasaki ◽  
Xaver Sewald ◽  
Walther Mothes ◽  
Pradeep D. Uchil
Keyword(s):  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Cell Types ◽  
Innate Immune ◽  
Type I ◽  
Toll Like Receptor ◽  
Viral Spread ◽  
Immune Sensing ◽  
Innate Immune Sensing ◽  
Murine Leukemia

ABSTRACT Lymph-borne Friend murine leukemia virus (FrMLV) exploits the sentinel macrophages in the draining popliteal lymph node (pLN) to infect highly permissive innate-like B-1 cells and establish infection in mice. The reason for FrMLV sensitivity of B-1 cells and their impact on viral spread is unknown. Here we demonstrate that Toll-like receptor 7 (TLR7) sensing and type I interferon (IFN-I) signaling in B-1 cells contribute to FrMLV susceptibility. FrMLV infection in B-1 cell-deficient mice (bumble; IκBNS dysfunctional) was significantly lower than that in the wild-type mice and was rescued by adoptive transfer of wild-type B-1 cells. This rescue of FrMLV infection in bumble mice was dependent on intact TLR7 sensing and IFN-I signaling within B-1 cells. Analyses of infected cell types revealed that the reduced infection in bumble mice was due predominantly to compromised virus spread to the B-2 cell population. Our data reveal how FrMLV exploits innate immune sensing and activation in the B-1 cell population for infection and subsequent spread to other lymphocytes. IMPORTANCE Viruses establish infection in hosts by targeting highly permissive cell types. The retrovirus Friend murine leukemia virus (FrMLV) infects a subtype of B cells called B-1 cells that permit robust virus replication. The reason for their susceptibility had remained unknown. We found that innate sensing of incoming virus and the ensuing type I interferon response within B-1 cells are responsible for their observed susceptibility. Our data provide insights into how retroviruses coevolved with the host to co-opt innate immune sensing pathways designed to fight virus infections for establishing infection. Understanding early events in viral spread can inform antiviral intervention strategies that prevent the colonization of a host.

scholarly journals Type I interferon response and innate immune sensing of cancer

2013 ◽  
Vol 34 (2) ◽  
pp. 67-73 ◽  
Author(s):  
Mercedes B. Fuertes ◽  
Seng-Ryong Woo ◽  
Byron Burnett ◽  
Yang-Xin Fu ◽  
Thomas F. Gajewski
Keyword(s):  
Type I Interferon ◽  
Innate Immune ◽  
Interferon Response ◽  
Type I ◽  
Immune Sensing ◽  
Innate Immune Sensing
Sign in / Sign up

Export Citation Format

Share Document