Toll-like receptors (TLRs) are essential for activation of the innate immune system in response to invading pathogens. TLR14, which is unique to fish, has been identified in several fish species, but its function is unclear. In this study, Japanese flounder (Paralichthys olivaceus) TLR14 gene (JfTLR14) was cloned and its expression profiles were analyzed after infection with viral hemorrhagic septicemia virus, gram-positive Streptococcus iniae and gram-negative Edwardsiella tarda. The coding region of JfTLR14 cDNA was 2,607 bp, encoding 878 amino acid residues. JfTLR14 was highly expressed in head kidney of healthy flounder. In response to infection with VHSV and S. iniae, the JfTLR14 gene was up-regulated at only 1 day post-infection (dpi). However, E. tarda infection increased JfTLR14 gene expression from 1 to 6 dpi. These results imply that JfTLR14 participates more in the immune response against E. tarda infection than in the immune responses to other pathogen infections.
"In the Japanese flounder, TLR14, which has not yet been detected in mammals, is induced more strongly after E. tarda infection than after Streptococcus iniae infection or virus infection (Hwang et al., 2011). Recently, expression of TLR5S was shown to be induced during pathogen infection of Atlantic salmon (Tsoi et al., 2006) and olive flounder (Moon et al., 2011), suggesting that TLR5S is an important PRR that responds to bacterial infection and regulates acute immunity in fish. "
[Show abstract][Hide abstract] ABSTRACT: The acute-phase response (APR) is an important systemic reaction that occurs within hours of an inflammatory signal caused by physical bodily injury or microbial infection. To investigate the APR of the olive flounder (Paralichthys olivaceus) following infection with a pathogen, we established an expressed sequence tag (EST)-based cDNA microarray chip composed of 13,061 PCR-amplified cDNAs encoding unique genes selected from an olive flounder EST analysis. Microarray analyses showed that the set of genes involved in the APR was strongly up-regulated in the liver of the olive flounder after infection with Edwardsiella tarda. Among the up-regulated genes, catechol-O-methyltransferase domain-containing protein 1, six-transmembrane prostate protein, haptoglobin precursor, and toll-like receptor 5 soluble form were particularly strongly up-regulated. Interestingly, the toll-like receptor 5 soluble form, which has not yet been detected in mammals, was up-regulated as much as 250-fold upon E. tarda infection. These results suggest that the APR mechanism of fish may be regulated differently from that of mammals. The data described here contribute toward our collective understanding of APR, especially in fish.
"There are no homologs of mammalian TLR6 or -10 in teleosts   , indicating that they evolved later (Table 1)  . The fish TLR14 genes have been classified as homologs of the mammalian TLR2 subfamily because TLR14 is located closest to the TLR2 cluster, suggesting that it evolved from an ancestor of TLR2 prior to the divergence of agnathans and teleosts  . Thus, TLR14 might be a functional substitute for mammalian TLR6 and -10. "
[Show abstract][Hide abstract] ABSTRACT: During the past decade, huge progress has been made in research into teleost PAMPs (pathogen-associated molecule patterns) recognition receptors (PRRs). Numerous fish PRR genes have been identified, and the primordial functions of PRRs involved in the innate immune response to viral infection (especially those responsible for sensing viral RNA) have been increasingly clarified in teleosts. Particular progress has been made in our understanding of Toll-like receptors (TLRs) and retinoic acid inducible gene I (RIG-I)-like receptors (RLRs). However, there are important evolutionary differences between teleosts and mammals; for instance, seven TLR repertoires (TLR5S, -14, -19, -20, -21, -22 and -23) are present in teleosts but not in mammals, indicating that some TLRs likely possess different functions. Thus, comparison of PRRs in teleosts and mammals may help us understand the immune responses triggered by host-pathogen interactions in teleosts. In this article, the evolutionary conservations and divergences in the PRR mechanisms of teleosts and mammals are examined, with a focus on their molecular features and the recognition of viral RNA by fish TLRs and RLRs. In addition, the mechanism of type I interferon gene expression in teleosts, which is enhanced after the recognition of viral RNA by fish TLRs and RLRs, is also introduced.
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