Toll‐Like Receptor 3: A Link between Toll‐Like Receptor, Interferon and Viruses

Matsumoto, Misako; Funami, Kenji; Oshiumi, Hiroyuki; Seya, Tsukasa

doi:10.1111/j.1348-0421.2004.tb03500.x

Cited by 174 publications

(141 citation statements)

References 57 publications

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“…The gill is a potential port of entry for infectious agents; hence, inducible expression of Mx in gill might represent a critical protection mechanism against virus invasion. In mammals, TLR3 is strongly associated with the antiviral response via dsRNA intermediate during viral replication (Alexopoulou et al 2001;Matsumoto et al 2004;Oshiumi et al 2003b), although a recent study by Edelmann et al (2004) questioned the universal antiviral nature of TLR3. While this work was in progress, a paper appeared describing the signal pathway from TLR3 to IFN and Mx induction in zebrafish (Sullivan et al 2007).…”

Section: Discussionmentioning

confidence: 99%

Toll-like receptor 3 regulates Mx expression in rare minnow Gobiocypris rarus after viral infection

Zhang

Wang

et al. 2008

Immunogenetics

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Toll-like receptor 3 (TLR3) plays a key role in activating immune responses during viral infection. To study the genes involved in the regulatory function of TLR3 in the rare minnow Gobiocypris rarus after viral infection, a full-length cDNA of TLR3 (GrTLR3) with a splice variant (GrTLR3s) was identified by homologous cloning and RACE techniques. The antiviral effector molecule Mx gene was cloned and partially sequenced. The mRNA expression levels of GrTLR3, GrTLR3s, and Mx were studied in different tissues before and after virus infection by real-time quantitative RT-PCR. The transcripts of all three genes in liver were significantly increased following GCRV infection (P<0.05). The mRNA levels in liver were upregulated at 24 h post-injection for GrTLR3 and GrTLR3s, and at 12 h for Mx. The upregulated expression levels were several folds for GrTLR3s, tens of folds for GrTLR3, and hundreds of folds for Mx. By semiquantitative RT-PCR, GrTLR3 and Mx expressed at all the developmental stages, whereas GrTLR3s could only be detected at later developmental stages. Using RNAi and transgenic techniques, GrTLR3 mediated Mx expression but GrTLR3s did not. The time-dependent upregulation of receptor and effector, and the Mx over-expression dependent on TLR3, indicated that GrTLR3 regulated Mx expression in viral infection through a configuration change in rare minnow, and its splice variant did not contribute to the process.

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Section: Discussionmentioning

confidence: 99%

Toll-like receptor 3 regulates Mx expression in rare minnow Gobiocypris rarus after viral infection

Zhang

Wang

et al. 2008

Immunogenetics

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“…TLR3 was found to recognize double-stranded RNA (dsRNA) and signal downstream to activate NFκB and the IFNβ promoter. [124][125][126][127][128][129] The crystal structure of the ectodomain (ligandbinding domain) of murine TLR3 has recently become available (Fig. 7).…”

Section: Intracellular Tlr3 Activation: Dsrna and Poly (I:c)mentioning

confidence: 99%

Potential adjuvantic properties of innate immune stimuli

et al. 2009

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Just as the prescient comment by Gaston Ramon was relegated to the last footnote of his 1926 paper, 1 so has research on the mechanisms of action of adjuvants, until recently, languished as parenthetical annotations and addenda in the archives of immunology and vaccine development. Ramon defined immunological adjuvants as "substances used in combination with a specific antigen that produced a more robust immune response than the antigen alone." Interestingly enough, he was referring to his empirical findings that the addition of bread crumbs, tapioca, saponin and 'starch oil' to antigenic preparations greatly enhanced antibody responses to diphtheria or tetanus. 2 A year later, the adjuvanticity of aluminum salts (primarily phosphate and hydroxide) was discovered by Glenny and coworkers. 3 In the 83 years that have elapsed, the repertoire of investigational adjuvants has grown to encompass a very wide range of materials, 4 but aluminum salt-based mineral salts (generically, and incorrectly, termed "alum") have remained the only adjuvants currently approved by the FDA. Aluminum salts have enjoyed a good safety record, but they are weak adjuvants for antibody induction and induce a T helper-2 (T H 2)-skewed, rather than a T helper-1 (T H 1) response. 5,6 Furthermore, not only are aluminum salts ineffective at inducing cytotoxic T lymphocyte (CTL) or mucosal IgA antibody responses, but also have a propensity to induce IgE responses, which have been associated with allergic reactions in some subjects. 5,6 Very recent reports implicate the Nalp3 inflammasome, a component of the innate immune response, as the effector limb of alum-associated adjuvanticity. [7][8][9] In 1962, Dresser observed that injection of purified soluble proteins not only failed to stimulate an immune response, but tolerized animals unless a bacterial extract was admixed with the protein immunogen. 10 This led him to redefine adjuvanticity as "a property of a substance which can act as a physiological switch, directing at least some immunologically competent cells to respond by making antibody rather than by becoming immunologically paralyzed by the antigen," 11 confirming Johnson's earlier observations that lipopolysaccharide (LPS) from Gram-negative bacteria exerted potent adjuvant properties, 12 and perhaps paved the way for the subsequent discovery of the wide range of microorganism-derived adjuvants. 13 TLRs are pattern recognition receptors present on diverse cell types that recognize specific molecular patterns present in molecules that are broadly shared by pathogens but distinguishable from host molecules, collectively referred to as pathogen-associated molecular patterns (PAMPs). 14,15 There are 10 TLRs in the human genome;

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“…on Macrophages Induced by Poly I:C. Expression of TLR3 was detected in macrophages, dendritic cells, and epithelial cells, and poly I:C stimulation could up-regulate TLR3 expression on all of these cells (29,30). RT-PCR analysis showed that TLR3 mRNA expression was also detected in the liver, peritoneal macrophages from C57BL͞6 mice, and RAW264.7 cells (data not shown).…”

Section: Blockade Of Tlr3 Prevented the Down-regulation Of Tlr4 Exprementioning

confidence: 99%

Toll-like receptor 3 ligand attenuates LPS-induced liver injury by down-regulation of toll-like receptor 4 expression on macrophages

Jiang

Sun

Wei

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

144

122

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Toll‐Like Receptor 3: A Link between Toll‐Like Receptor, Interferon and Viruses

Cited by 174 publications

References 57 publications

Toll-like receptor 3 regulates Mx expression in rare minnow Gobiocypris rarus after viral infection

Toll-like receptor 3 regulates Mx expression in rare minnow Gobiocypris rarus after viral infection

Potential adjuvantic properties of innate immune stimuli

Toll-like receptor 3 ligand attenuates LPS-induced liver injury by down-regulation of toll-like receptor 4 expression on macrophages

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