Immune Signaling by RIG-I-like Receptors

Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195-7650, USA.
Immunity (Impact Factor: 21.56). 05/2011; 34(5):680-92. DOI: 10.1016/j.immuni.2011.05.003
Source: PubMed


The RIG-I-like receptors (RLRs) RIG-I, MDA5, and LGP2 play a major role in pathogen sensing of RNA virus infection to initiate and modulate antiviral immunity. The RLRs detect viral RNA ligands or processed self RNA in the cytoplasm to trigger innate immunity and inflammation and to impart gene expression that serves to control infection. Importantly, RLRs cooperate in signaling crosstalk networks with Toll-like receptors and other factors to impart innate immunity and to modulate the adaptive immune response. RLR regulation occurs at a variety of levels ranging from autoregulation to ligand and cofactor interactions and posttranslational modifications. Abberant RLR signaling or dysregulation of RLR expression is now implicated in the development of autoimmune diseases. Understanding the processes of RLR signaling and response will provide insights to guide RLR-targeted therapeutics for antiviral and immune-modifying applications.

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Available from: Yueh-Ming Loo,
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    • "Simultaneous presence of high producer alleles of pro - inflammatory cyto - kine genes determines the genetic predisposition to depres - sion via upregulation of IDO , while impact of environmental stresses is mediated via hormonal activation of TDO ( Ox - enkrug , 2010 ) . Aberrant RIGI - like receptor ( RLR ) signaling or dysregu - lation of RLR expression have been implicated in the de - velopment of autoimmune diseases ( Loo and Gale , 2011 ) . In the present study , six proteins that play central roles in RLR signaling were differentially overexpressed : RIGI ( DDX58 ) , ISG15 , IFIH1 , IRF7 , CXCL8 , and MAPK13 . "
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    • "IFN produced and secreted as a result of the RLR cascade binds to the IFN receptor to regulate JAK- STAT signaling and the ISGF3-dependent expression of interferonstimulated genes (ISGs) encoding proteins, such as Mx1 [16e18], which possess direct antiviral activity [4] [19]. In addition, virus infection and signaling through the RLRs also induce the expression of various proinflammatory cytokines, for instance IL-1b [20], to control infection [4]. "
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    • "Complex assembly is responsible for the activation of the IKK and IKK-like kinases, which activate necrosis factor (NF)-kB and IRF3/7, respectively, resulting in the formation of the interferon beta (IFN-B) enhanceosome (Loo and Gale, 2011). Transcriptional induction of IFNB results in both autocrine and paracrine activation of the JAK/STAT pathway and the coordinated upregulation of $500 interferon-stimulated genes (ISGs) (Loo and Gale, 2011). In addition, many ISGs can also be directly induced in response to virus infection as a result of PRR detection and IRF3/7 activation (Honda et al., 2005; Schmid et al., 2010). "
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