Identification,phylogeny and expression analysis of suppressors of cytokine signaling in channel catfish

The suppressors of cytokine signaling (SOCS) family genes play important roles in regulating a variety of signal transduction pathways that are involved in immunity, growth and development. Because of their importance, they have been extensively studied in mammalian species, but they have not been systematically studied among teleost fish species. In this study, a total of 12 SOCS genes were characterized to understand the molecular mechanisms of SOCS function in channel catfish. Phylogenetic analyses suggested that all SOCS were clustered into two main clusters. Further syntenic analysis confirmed the phylogenetic analyses and allowed the annotation of SOCS genes in channel catfish. This work, for the first time, determined the expression profiles of the 12 SOCS genes after bacterial infections with Flavobacterium columnare and Edwardsiella ictaluri in channel catfish. The SOCS1a and SOCS3a were significantly up-regulated at 4 h after F. columnare challenge in the gill, but were down-regulated at later stages of pathogenesis. Similarly, SOCS1a and CISH were significantly up-regulated at 3 h in intestine under E. ictaluri infection, but were down-regulated at later stages of pathogenesis at 24 h and 3 days after infection. These expression patterns may indicate that SOCS genes could be induced in acute immune responses after bacterial infections, but the massive cytokine expression, especially chemokine expression after the first day of infection may have had negative feedback leading to the overall down-regulation of the expression of SOCS genes. Moreover, the differential expression patterns of SOCS genes in the catfish gill and intestine after F. columnare and E. ictaluri infection demonstrated that the regulation of SOCS gene expression was both tissue-specific and time-dependent. Taken together, these results suggested that SOCS genes were involved in immune responses to bacterial invasions, and these results set the foundation for future studies of SOCS gene functions.     

Therapeutic immunomodulation using a virus—the potential of inactivated orf virus

Viruses can manipulate the immune response against them by various strategies to influence immune cells, i.e. by over-activation leading to functional inactivation, bypassing antigen presentation or even suppression of effector functions. Little is known, however, about how these features of immune regulation and modulation could be used for therapeutic purposes. Reasons for this include the complexity of immune regulatory mechanisms under certain disease conditions and the risks that infections with viruses pose to human beings. The orf virus (ORFV), a member of the Parapoxvirus genus of the poxvirus family, is known as a common pathogen in sheep and goats worldwide. The inactivated ORFV, however, has been used as a preventative as well as therapeutic immunomodulator in veterinary medicine in different species. Here, we review the key results obtained in pre-clinical studies or clinical studies in veterinary medicine to characterise the therapeutic potential of inactivated ORFV. Inactivated ORFV has strong effects on cytokine secretion in mice and human immune cells, leading to an auto-regulated loop of initial up-regulation of inflammatory and Th1-related cytokines, followed by Th2-related cytokines that attenuate immunopathology. The therapeutic potential of inactivated ORFV has been recognised in several difficult-to-treat disease areas, such as chronic viral diseases, liver fibrosis or various forms of cancer. Further research will be required in order to evaluate the full beneficial potential of inactivated ORFV for therapeutic immunomodulation.     

Reprint of: The non-mammalian MIF superfamily

Macrophage migration inhibitory factor (MIF) was first described as a cytokine 50 years ago, and emerged in mammals as a pleiotropic protein with pro-inflammatory, chemotactic, and growth-promoting activities. In addition, MIF has gained substantial attention as a pivotal upstream mediator of innate and adaptive immune responses and with pathologic roles in several diseases. Of less importance in mammals is an intrinsic but non-physiologic enzymatic activity that points to MIF's evolution from an ancient defense molecule. Therefore, it is not surprising that mif-like genes also have been found across a range of different organisms including bacteria, plants, protozoa, helminths, molluscs, arthropods, fish, amphibians and birds. While Genebank analysis identifying mif-like genes across species is extensive, contained herein is an overview of the non-mammalian MIF-like proteins that have been most well studied experimentally. For many of these organisms, MIF contributes to an innate defense system or plays a role in development. For parasitic organisms however, MIF appears to function as a virulence factor aiding in the establishment or persistence of infection by modulating the host immune response. Consequently, a combined targeting of both parasitic and host MIF could lead to more effective treatment strategies for parasitic diseases of socioeconomic importance.     

The non-mammalian MIF superfamily

Macrophage migration inhibitory factor (MIF) was first described as a cytokine 50 years ago, and emerged in mammals as a pleiotropic protein with pro-inflammatory, chemotactic, and growth-promoting activities. In addition, MIF has gained substantial attention as a pivotal upstream mediator of innate and adaptive immune responses and with pathologic roles in several diseases. Of less importance in mammals is an intrinsic but non-physiologic enzymatic activity that points to MIF’s evolution from an ancient defense molecule. Therefore, it is not surprising that mif-like genes also have been found across a range of different organisms including bacteria, plants, ‎protozoa, helminths, molluscs, arthropods, fish, amphibians and birds. While Genebank analysis identifying mif-like genes across species is extensive, contained herein is an overview of the non-mammalian MIF-like proteins that have been most well studied experimentally. For many of these organisms, MIF contributes to an innate defense system or plays a role in development. For parasitic organisms however, MIF appears to function as a virulence factor aiding in the establishment or persistence of infection by modulating the host immune response. Consequently, a combined targeting of both parasitic and host MIF could lead to more effective treatment strategies for parasitic diseases of socioeconomic importance.