Article

Evidence for evolving Toll-IL-1 receptor-containing adaptor molecule function in vertebrates.

Department of Biochemistry, Microbiology, and Molecular Biology, University of Maine, Orono, ME 04469, USA.
The Journal of Immunology (Impact Factor: 5.36). 05/2007; 178(7):4517-27. DOI: 10.4049/jimmunol.178.7.4517
Source: PubMed

ABSTRACT In mammals, Toll-IL-1R-containing adaptor molecule 1 (TICAM1)-dependent TLR pathways induce NF-kappaB and IFN-beta responses. TICAM1 activates NF-kappaB through two different pathways involving its interactions with TNFR-associated factor 6 and receptor-interacting protein 1. It also activates IFN regulatory factor 3/7 through its interaction with TANK-binding kinase-1, leading to the robust up-regulation of IFN-beta. In this study, we describe the role of zebrafish (Danio rerio) TICAM1 in activating NF-kappaB and zebrafish type I IFN. Zebrafish IFN is unique in that it cannot be categorized as being alpha- or beta-like. Through comprehensive sequence, phylogenetic, and syntenic analyses, we fully describe the identification of a zebrafish TICAM1 ortholog. Zebrafish TICAM1 exhibits sequence divergence from its mammalian orthologs and our data demonstrate that these sequence differences have functional consequences. Zebrafish TICAM1 activates zebrafish IFN; however, it does so in an apparently IFN regulatory factor 3/7-independent manner. Furthermore, zebrafish TICAM1 does not interact with zebrafish TNFR-associated factor 6, thus NF-kappaB activation is dependent upon its interaction with receptor-interacting protein 1. Comparative genome analysis suggests that TICAM1 and TICAM2 evolved from a common vertebrate TICAM ancestor following a gene duplication event and that TICAM2 was lost in teleosts following the divergence of the rayfin and lobefin fishes 450 million years ago. These studies provide evidence, for the first time, of the evolving function of a vertebrate TLR pathway.

Full-text

Available from: Carol H Kim, Apr 26, 2015
0 Followers
 · 
103 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Global fish production from aquaculture has rapidly grown over the past decades, and grass carp shares the largest portion. However, hemorrhagic disease caused by grass carp reovirus (GCRV) results in tremendous loss of grass carp (Ctenopharyngodon idella) industry. During the past years, development of molecular biology and cellular biology technologies has promoted significant advances in the understanding of the pathogen and the immune system. Immunoprophylaxis based on stimulation of the immune system of fish has also got some achievements. In this review, authors summarize the recent progresses in basic researches on GCRV; viral nucleic acid sensors, high-mobility group box proteins (HMGBs); pattern recognition receptors (PRRs), Toll-like receptors (TLRs) and retinoic acid inducible gene I-(RIG-I-) like receptors (RLRs); antiviral immune responses induced by PRRs-mediated signaling cascades of type I interferon (IFN-I) and IFN-stimulated genes (ISGs) activation. The present review also notices the potential applications of molecule genetic markers. Additionally, authors discuss the current preventive and therapeutic strategies (vaccines, RNAi, and prevention medicine) and highlight the importance of innate immunity in long term control for grass carp hemorrhagic disease.
    Journal of Immunology Research 02/2015; 2015:Article ID 670437. DOI:10.1155/2015/670437 · 2.93 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Melanoma Differentiation-Associated protein 5 (MDA5) is a member of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family, which are cytosolic pattern recognition receptors that detect viral nucleic acids. Here we show an Mda5-dependent response to rhabdovirus infection in vivo using a dominant-negative mda5 transgenic zebrafish. Dominant-negative mda5 zebrafish embryos displayed an impaired antiviral immune response compared to wild-type counterparts that can be rescued by recombinant full-length Mda5. To our knowledge, we have generated the first dominant-negative mda5 transgenic zebrafish and demonstrated a critical role for Mda5 in the antiviral response to rhabdovirus. Copyright © 2015. Published by Elsevier Ltd.
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this study, the gene and promoter sequences of turbot Scophthalmus maximus (Sm) toll-like receptor 3 (Tlr3) were cloned and its mRNA tissue distribution and gene expression in response to polyinosinic:polycytidylic acid (poly I:C) and turbot reddish body iridovirus (TRBIV) challenges were studied in vivo. The smtlr3 gene spans over 4·4 kb with a structure of five exons–four introns and encodes a peptide of 916 amino acids. The putative protein shares the highest sequence identity of 52·8–78·5% with fish Tlr3 and contains a signal peptide sequence, 13 leucine-rich repeat (LRR) motifs, a transmembrane region and a toll/interleukin-1 receptor (TIR) domain. Phylogenetic analysis grouped it with other teleost Tlr3s. A number of transcription factor binding sites were identified in the 1538 bp 5′ flanking region of smtlr3, including interferon-stimulated response element (ISRE) and those for interferon regulatory factors (IRF) and signal transducer and activator of transcriptions (STATs) smtlr3 transcripts were expressed ubiquitously with higher levels in the head kidney, heart and digestion organs. They were up-regulated by both poly I:C and TRBIV in immune and non-immune organs, but most strongly in the head kidney. Finally, the smtlr3 exhibited a two-wave induced expression during a five day time course when exposure of S. maximus to poly I:C. These findings provide insights into the role of SmTlr3 in antiviral response.
    Journal of Fish Biology 01/2015; DOI:10.1111/jfb.12559 · 1.73 Impact Factor