What is known about the biological activity of fish cytokines is reviewed. Most of the functional studies performed to date have been in teleost fish, and have focused on the induced effects of cytokine recombinant proteins, or have used loss- and gain-of-function experiments in zebrafish. Such studies begin to tell us about the role of these molecules in the regulation of fish immune responses and whether they are similar or divergent to the well-characterised functions of mammalian cytokines. This knowledge will aid our ability to determine and modulate the pathways leading to protective immunity, to improve fish health in aquaculture.

The Function of Fish Cytokines

Summary
Retinoic acid-inducible gene I (RIG-I) -like receptors (RLRs) are found conservatively present in teleost fish. All three members, RIG-I, MDA5 and LGP2, together with the downstream molecules such as MITA, TRAF3 and TBK1, have been identified in a range of fish species. However, it is unexpected that RIG-I has not been reported in fish of Acanthopterygii, and it would be important to clarify the presence and role of the RIG-I gene in a broad range of taxa in Teleostei. RLRs in fish can be induced in vivo and in vitro by viral pathogens as well as synthetic dsRNA, poly(I:C), leading to the production of type I interferons (IFNs) and the expression of IFN-stimulated genes (ISGs). Bacterial pathogens, such as Edwardsiella tarda, and their components, such as lipopolysaccharide are also found to induce the expression of RLRs, and whether such induction was mediated through the direct recognition by RLRs or through crosstalk with other pattern recognition receptors recognizing directly bacterial pathogen-associated molecular patterns awaits to be investigated. On the other hand, RLR-activated type I IFN production can be negatively regulated in fish by molecules, such as TBK-1-like protein and IRF10, which are found to negatively regulate RIG-I and MAVS-activated type I IFN production, and to block MITA or bind ISRE motifs, respectively. It is considered that the evolutionary occurrence of RLRs in fish, and their recognized ligands, especially those from their fish pathogens, as well as the mechanisms involved in the RLR signalling pathways, are of significant interest for further investigation.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/imm.12714

Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) in fish: current knowledge and future perspectives.

Interferons (IFNs) have been reported in vertebrates from fish to mammals. To date, two types of IFNs, i.e. type I and type II IFNs have been reported in a range of fish species in aquaculture. In fish, type I IFNs are clarified into group I and group II, with two cysteines and four cysteines, and further into subgroups a, d, e, h, and b, c, f, respectively. Group I IFNs appear to exist in all fish species, whereas group II IFNs are discovered only in certain species such as cyprinids, salmonids and perciform fish. It seems preferentially functional that group I IFNs signal through cytokine receptor family B (CRFB) 5 and CRFB1, while group II IFNs through CRFB5 and CRFB2. But they all initiate a same signalling pathway for the expression of interferon induced genes. The information about the production and the function of type I IFNs in fish are further summarized in the review. Interestingly, two members of type II IFNs, IFN-gamma and a unique member, IFN-gamma related gene (IFN-gamma rel) exist in fish, and IFN-gamma and IFN-gamma rel can separately become homodimers for signalling through CRFB13, CRFB17, CRFB6 and CRFB17, respectively. In addition, the variation in the composition of type I and type II IFNs as well as in their receptors in some cyprinid and salmonid fish has also been reviewed. It is suggested that future perspectives for the research on type I and type II IFNs in fish are outlined from a comparative and evolutionary point of view.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/raq.12349

Fish type I and type II interferons: composition, receptor usage, production and function

Pattern recognition receptors (PRRs) are a class of immune sensors that play crucial roles in detecting and responding to the conserved patterns of microorganisms. To date, many PRRs, such as TLRs, RLRs and NLRs, as well as their downstream molecules have been identified and characterized in teleost, while their ligands and immunoregulatory mechanisms remain largely unknown. In the present review, we described and discussed the main members of TLR/RLR/NLR families, including their expression profiles, signaling transductions and functions in teleost. And some splicing isoforms from TLR/RLR/NLR families were also addressed, which play synergistic and/or antagonistic roles in response to pathogen infections in teleost. TLRs sense different pathogens by forming homodimer and/or heterodimer. Beyond, functions of TLRs can also be affected by migrating. And some endolysosomal TLRs undergo proteolytic cleavage and in a pH-dependent mechanism to attain a mature functional form that mediate ligand recognition and downstream signaling. Until now, more than 80 members in TLR/RLR/NLR families have been identified in teleost, while only TLR5, TLR9, TLR19, TLR21, TLR22, MDA5, LGP2, NOD1 and NOD2 have direct evidence of ligand recognition in teleost. Meanwhile, new ligands as well as signaling pathways do occur during evolution of teleost. This review summarizes progresses on the TLRs/RLRs/NLRs in teleost. We attempt to insight into the ligands recognition and signaling transmission of TLRs/RLRs/NLRs in teleost.

Progresses on three pattern recognition receptor families (TLRs, RLRs and NLRs) in teleost

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