Abstract
TIR domain-containing adaptor-inducing interferon-β (TRIF), a cytosolic adaptor protein, plays a key role in the mammalian toll-like receptor-mediated signaling pathway. However, the role of TRIF in large yellow croaker (LcTRIF) remains poorly understood. The main objective of this study was to explore the role of LcTRIF in triggering antiviral immune responses and the potential function of LcTRIF in regulating lipid metabolism. In the present study, the full-length coding sequence of TRIF from large yellow croaker was cloned and characterized. In vivo, upon poly (I:C) stimulation, the transcriptional levels of LcTRIF were rapidly elevated in immune-related tissues at the early stage of injection. In vitro, the MRNA expression of LcTRIF was significantly but not dramatically upregulated in macrophages treated with poly (I:C). Activation of LcTRIF by poly (I:C) significantly increased the transcription of genes involved in inflammatory responses, and this induction was blocked by knockdown of LcTRIF. Moreover, the ability of LcTRIF to induce inflammatory responses may partially be attributed to the promotion of mRNA expression of IFNh and NF-κB pathway genes. In addition, activation of the LcTRIF-mediated pathway inhibited the increase in hepatic stearoyl-coenzyme A (CoA) desaturase 1 induced by palmitic acid and subsequently alleviated lipid accumulation in hepatocytes. These results revealed the crucial role of LcTRIF in triggering antiviral immune responses and the unconventional metabolic function of LcTRIF in regulating hepatic lipogenesis in large yellow croaker.
Highlights
Toll-like receptors (TLRs), one of the most extensively studied pattern-recognition receptors (PRRs), play a crucial role in both the innate immune system and the adaptive immune system by recognizing conserved components of pathogens referred to as pathogen associated molecular patterns (PAMPs) [1, 2]
The full-length cDNA of LcTRIF (GenBank Accession No: MH820380.1) was 3,012 bp and contained a 5′ untranslated terminal region (UTR) of 438 bp, a 3′ UTR of 768 bp, and an open reading frame (ORF) of 1,806 bp encoding a polypeptide of 601 amino acids, which exhibited the typical characteristics of a TIR domain (351–471 aa) close to its C terminus
Multiple sequence alignment of the TIR domain of large yellow croaker TIR domaincontaining adaptor-inducing interferon-β (TRIF) with that of other species found that LcTRIF had three highly conserved regions: box 1 (YN), box 2 (EDFQVPG), and box 3 (IFAR) (Figure 2)
Summary
Toll-like receptors (TLRs), one of the most extensively studied pattern-recognition receptors (PRRs), play a crucial role in both the innate immune system and the adaptive immune system by recognizing conserved components of pathogens referred to as pathogen associated molecular patterns (PAMPs) [1, 2]. TRIF, known as TIR domain-containing adapter molecule 1 (TICAM-1), is unique to TLR3-and TLR4-mediated signaling pathways, which activate interferon (IFN) regulatory factors 3/7 (IRF3/7) and nuclear factor-kappa B (NF-κB) and induce the production of type I IFN and inflammatory cytokines, leading to direct killing of invading pathogens [5,6,7]. In teleosts, TRIF lacks both the N-terminal and the C-terminal proline-rich domains and the proline in box of the TIR domain, which suggests that fish TRIF activates type I IFN and NF-κB through different ways with its mammalian TRIF orthologs [16,17,18,19] These findings revealed a real difference in TRIF-mediated antiviral immune responses between teleosts and mammals. The unconventional function of the TRIFmediated pathway in regulating lipid metabolism has not been reported in fish
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