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      Toll-Like Receptors and Myocardial Inflammation

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      International Journal of Inflammation
      SAGE-Hindawi Access to Research

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          Abstract

          Toll-like receptors (TLRs) are a member of the innate immune system. TLRs detect invading pathogens through the pathogen-associated molecular patterns (PAMPs) recognition and play an essential role in the host defense. TLRs can also sense a large number of endogenous molecules with the damage-associated molecular patterns (DAMPs) that are produced under various injurious conditions. Animal studies of the last decade have demonstrated that TLR signaling contributes to the pathogenesis of the critical cardiac conditions, where myocardial inflammation plays a prominent role, such as ischemic myocardial injury, myocarditis, and septic cardiomyopathy. This paper reviews the animal data on (1) TLRs, TLR ligands, and the signal transduction system and (2) the important role of TLR signaling in these critical cardiac conditions.

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          Most cited references124

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          Recognition of single-stranded RNA viruses by Toll-like receptor 7.

          Viral infection of mammalian host results in the activation of innate immune responses. Toll-like receptors (TLRs) have been shown to mediate the recognition of many types of pathogens, including viruses. The genomes of viruses possess unique characteristics that are not found in mammalian genomes, such as high CpG content and double-stranded RNA. These genomic nucleic acids serve as molecular signatures associated with viral infections. Here we show that TLR7 recognizes the single-stranded RNA viruses, vesicular stomatitis virus and influenza virus. The recognition of these viruses by plasmacytoid dendritic cells and B cells through TLR7 results in their activation of costimulatory molecules and production of cytokines. Moreover, this recognition required intact endocytic pathways. Mice deficient in either the TLR7 or the TLR adaptor protein MyD88 demonstrated reduced responses to in vivo infection with vesicular stomatitis virus. These results demonstrate microbial ligand recognition by TLR7 and provide insights into the pathways used by the innate immune cells in the recognition of viral pathogens.
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            The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults.

            The cytokine-induced activation cascade of NF-kappaB in mammals and the activation of the morphogen dorsal in Drosophila embryos show striking structural and functional similarities (Toll/IL-1, Cactus/I-kappaB, and dorsal/NF-kappaB). Here we demonstrate that these parallels extend to the immune response of Drosophila. In particular, the intracellular components of the dorsoventral signaling pathway (except for dorsal) and the extracellular Toll ligand, spätzle, control expression of the antifungal peptide gene drosomycin in adults. We also show that mutations in the Toll signaling pathway dramatically reduce survival after fungal infection. Antibacterial genes are induced either by a distinct pathway involving the immune deficiency gene (imd) or by combined activation of both imd and dorsoventral pathways.
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              MD-2, a Molecule that Confers Lipopolysaccharide Responsiveness on Toll-like Receptor 4

              Toll-like receptor 4 (TLR4) is a mammalian homologue of Drosophila Toll, a leucine-rich repeat molecule that can trigger innate responses against pathogens. The TLR4 gene has recently been shown to be mutated in C3H/HeJ and C57BL/10ScCr mice, both of which are low responders to lipopolysaccharide (LPS). TLR4 may be a long-sought receptor for LPS. However, transfection of TLR4 does not confer LPS responsiveness on a recipient cell line, suggesting a requirement for an additional molecule. Here, we report that a novel molecule, MD-2, is requisite for LPS signaling of TLR4. MD-2 is physically associated with TLR4 on the cell surface and confers responsiveness to LPS. MD-2 is thus a link between TLR4 and LPS signaling. Identification of this new receptor complex has potential implications for understanding host defense, as well as pathophysiologic, mechanisms.
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                Author and article information

                Journal
                Int J Inflam
                IJI
                International Journal of Inflammation
                SAGE-Hindawi Access to Research
                2090-8040
                2042-0099
                2011
                29 September 2011
                : 2011
                : 170352
                Affiliations
                Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
                Author notes

                Academic Editor: Masanori Aikawa

                Article
                10.4061/2011/170352
                3182762
                21977329
                e9fe65c5-b6dc-4dca-b574-e29f3111d610
                Copyright © 2011 Y. Feng and W. Chao.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 2 April 2011
                : 24 May 2011
                : 12 June 2011
                Categories
                Review Article

                Immunology
                Immunology

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