Pathogen Recognition and Activation of the Innate Immune Response in Zebrafish

Abstract

<jats:p>The zebrafish has proven itself as an excellent model to study vertebrate innate immunity. It presents us with possibilities for<jats:italic>in vivo</jats:italic>imaging of host-pathogen interactions which are unparalleled in mammalian model systems. In addition, its suitability for genetic approaches is providing new insights on the mechanisms underlying the innate immune response. Here, we review the pattern recognition receptors that identify invading microbes, as well as the innate immune effector mechanisms that they activate in zebrafish embryos. We compare the current knowledge about these processes in mammalian models and zebrafish and discuss recent studies using zebrafish infection models that have advanced our general understanding of the innate immune system. Furthermore, we use transcriptome analysis of zebrafish infected with<jats:italic>E. tarda, S. typhimurium</jats:italic>, and<jats:italic>M. marinum</jats:italic>to visualize the gene expression profiles resulting from these infections. Our data illustrate that the two acute disease-causing pathogens,<jats:italic>E. tarda</jats:italic>and<jats:italic>S. typhimurium</jats:italic>, elicit a highly similar proinflammatory gene induction profile, while the chronic disease-causing pathogen,<jats:italic>M. marinum</jats:italic>, induces a weaker and delayed innate immune response.</jats:p>

Transforming Growth Factor (TGF)-β-activated Kinase 1 (TAK1) Activation Requires Phosphorylation of Serine 412 by Protein Kinase A Catalytic Subunit α (PKACα) and X-linked Protein Kinase (PRKX)

“…Components of the main innate immune signaling pathways, such as the major pattern recognition receptors, key adaptor proteins (such as MyD88 and TNF receptor-associated factors in the TLR and IL-1R pathways), and the downstream transcription factors NF-B and AP1 are all found to be highly conserved among humans, mice, and zebrafish. This finding strongly implies that similar signal transduction mechanisms exist among the three species (28,29). Particularly, the mammalian essential kinases TAK1 and IKK complexes in the TLR and IL-1R signaling pathways display the most apparent orthologies in zebrafish (29), although functional data are not yet derived.…”

“…Zebrafish (Danio rerio) is increasingly becoming a unique in vivo model system to study infectious, innate immune and inflammatory responses that can complement studies in mouse and human cell lines (27,28). Components of the main innate immune signaling pathways, such as the major pattern recognition receptors, key adaptor proteins (such as MyD88 and TNF receptor-associated factors in the TLR and IL-1R pathways), and the downstream transcription factors NF-B and AP1 are all found to be highly conserved among humans, mice, and zebrafish.…”

Toll-like receptor 9 and 21 have different ligand recognition profiles and cooperatively mediate activity of CpG-oligodeoxynucleotides in zebrafish

“…In acute cases, other signs may include ventral skin hyperemia and accumulation of red-colored ascitic fluid in the peritoneal cavity (33). E. tarda infection has been established as a model for studying microbial infection in zebrafish (34,35). We adopted this model to further investigate the function of zebTLR9 and zebTLR21 in mediating the antimicrobial activity of CpG-ODNs.…”

Hyperinsulinemia induces insulin resistance and immune suppression via Ptpn6/Shp1 in zebrafish

“…4). In addition, to further understand the effects on the innate immune system, we analyzed the expression of genes coding for important cytokines and for signal mediators and transcription regulators previously demonstrated to be relevant to the immune response (van der Vaart et al 2012, Meijer et al 2014. Strikingly, our data showed that all the genes studied in this context were downregulated at 4 hpi, except ptpn6, cxcr3.1, cxcr4b, and irf5 (Fig.…”