Teleost Chemokines and Their Receptors

Abstract

Chemokines are a superfamily of cytokines that appeared about 650 million years ago, at the emergence of vertebrates, and are responsible for regulating cell migration under both inflammatory and physiological conditions. The first teleost chemokine gene was reported in rainbow trout in 1998. Since then, numerous chemokine genes have been identified in diverse fish species evidencing the great differences that exist among fish and mammalian chemokines, and within the different fish species, as a consequence of extensive intrachromosomal gene duplications and different infectious experiences. Subsequently, it has only been possible to establish clear homologies with mammalian chemokines in the case of some chemokines with well-conserved homeostatic roles, whereas the functionality of other chemokine genes will have to be independently addressed in each species. Despite this, functional studies have only been undertaken for a few of these chemokine genes. In this review, we describe the current state of knowledge of chemokine biology in teleost fish. We have mainly focused on those species for which more research efforts have been made in this subject, specially zebrafish (Danio rerio), rainbow trout (Oncorhynchus mykiss) and catfish (Ictalurus punctatus), outlining which genes have been identified thus far, highlighting the most important aspects of their expression regulation and addressing any known aspects of their biological role in immunity. Finally, we summarise what is known about the chemokine receptors in teleosts and provide some analysis using recently available data to help characterise them more clearly.

Keywords: chemokines; fish; ligands; receptors; teleost.

Figure 1

Phylogenetic analysis of human CCR6, 7, 8, 9, 10 and ACKR4 (CCR11) amino acid sequences with identified teleost, reptile, bird, amphibian and cartilaginous fish sequences. Accession numbers of each sequence are included in the figure. Sequences were found by using the FASTA [108] and BLAST [109] suite of programs to search the non-redundant protein sequence database at NCBI. Phylogenetic relationships were constructed from ClustalX v1.81 [110] generated alignments of amino acid sequences using the neighbor-joining method [111], with values <75% shown. The tree was drawn using TreeView v1.6.1 [112] and bootstrapped 1000 times [113]. A different colour is used to indicate the clear clustering of sequences into each receptor group. Boxed regions indicate where there has been an expansion of a particular receptor, within teleosts.

Figure 2

Phylogenetic analysis of human CCR1, 2, 3, 4, 5 and 8 amino acid sequences (highlighted in blue) with identified teleost, reptile, bird, amphibian and cartilaginous fish sequences. Accession numbers of each sequence are included in the figure. Sequences were found and trees generated as described in Figure 1. A different colour is used to indicate the clear clustering of teleost sequences into specific groups. Each non-mammalian sequence was analysed by BLAST and the name reflects the top three mammalian CCR receptors it had highest similarity to. Sequences highlighted in red, indicate those sequences that had been given the name CCR3, CCR11 or 12 in the literature.

Figure 3

Phylogenetic analysis of human CXCR1, -2, -3, -4, -5, -6, -8 and ACKR3 (CXCR7) amino acid sequences with identified teleost, reptile, bird, amphibian and cartilaginous fish sequences. Accession numbers of each sequence are included in the figure, except where they have been predicted (PRED) using the available genome. Sequences were found and trees generated as described in Figure 1. A different colour is used to indicate the clear clustering of sequences into each receptor group. Boxed regions indicate where there has been an expansion of a particular receptor, within teleosts.

Figure 4

Synteny analysis of the locus containing the CXCR3 gene from human, reptile, amphibian, coelacanth and a selection of teleosts. Genscan [122], BLAST [109] and FASTA [108] were used to analyse the genomes of non-mammalian species to discover the gene order. Three copies of the CXCR3 genes clearly exist in all of the teleost genomes, except platyfish, where four seem to exist.

Figure 5

Phylogenetic analysis of human XCR1, CX3CR1, ACKR1 (DARC), ACKR2 (CCBP2), ACKR5 (CCRL2) and ACKR6 (PITPNM3) amino acid sequences with identified teleost, reptile, bird, amphibian and cartilaginous fish sequences. Sequences were found and trees generated as described in Figure 1. A different colour is used to indicate the clear clustering of sequences into each receptor group. Boxed regions indicate where there has been an expansion of a particular receptor, within teleosts.