Co-infections are very common in nature and occur when hosts are infected by two or more different pathogens either by simultaneous or secondary infections so that two or more infectious agents are active together in the same host. Co-infections have a fundamental effect and can alter the course and the severity of different fish diseases. However, co-infection effect has still received limited scrutiny in aquatic animals like fish and available data on this subject is still scarce. The susceptibility of fish to different pathogens could be changed during mixed infections causing the appearance of sudden fish outbreaks. In this review, we focus on the synergistic and antagonistic interactions occurring during co-infections by homologous or heterologous pathogens. We present a concise summary about the present knowledge regarding co-infections in fish. More research is needed to better understand the immune response of fish during mixed infections as these could have an important impact on the development of new strategies for disease control programs and vaccination in fish.

CD4 is a nonpolymorphic transmembrane glycoprotein molecule that is expressed on the surface of T-helper cells and plays an essential role in the immune response. It functions as a coreceptor with the T-cell receptor by binding to major histocompatibility complex class II on the surface of dendritic cells that present antigens. CD4+ T cells hold a key position in coordinating the immune system through production of several cytokines after activation and differentiation. The CD4+ T helper subtypes (T-helper 1, T-helper 2, T-helper 17, T-helper 9, and regulatory-T cells) perform different immune functions subsequent to their differentiation from the naive T cells. Different types of CD4+ T cells require different cytokines such as drivers and effectors, as well as master transcription factors for their activation. Fish cells that express CD4-related genes are activated in the presence of a pathogen and release cytokines against the pathogen. This review highlights the types of CD4+ T cells in fish and describes their direct role in cell-mediated and humoral immunity for protection against the intracellular bacterial as well as viral infections in fish.

In recent years, with the advent of next-generation sequencing along with the development of various bioinformatics tools, RNA sequencing (RNA-Seq)-based transcriptome analysis has become much more affordable in the field of biological research. This technique has even opened up avenues to explore the transcriptome of non-model organisms for which a reference genome is not available. This has made fish health researchers march towards this technology to understand pathogenic processes and immune reactions in fish during the event of infection. Recent studies using this technology have altered and updated the previous understanding of many diseases in fish. RNA-Seq has been employed in the understanding of fish pathogens like bacteria, virus, parasites, and oomycetes. Also, it has been helpful in unraveling the immune mechanisms in fish. Additionally, RNA-Seq technology has made its way for future works, such as genetic linkage mapping, quantitative trait analysis, disease-resistant strain or broodstock selection, and the development of effective vaccines and therapies. Until now, there are no reviews that comprehensively summarize the studies which made use of RNA-Seq to explore the mechanisms of infection of pathogens and the defense strategies of fish hosts. This review aims to summarize the contemporary understanding and findings with regard to infectious pathogens and the immune system of fish that have been achieved through RNA-Seq technology.

Enteric redmouth disease (ERM) is a serious septicemic bacterial disease of salmonid fish species. It is caused by Yersinia ruckeri, a Gram-negative rod-shaped enterobacterium. It has a wide host range, broad geographical distribution, and causes significant economic losses in the fish aquaculture industry. The disease gets its name from the subcutaneous hemorrhages, it can cause at the corners of the mouth and in gums and tongue. Other clinical signs include exophthalmia, darkening of the skin, splenomegaly and inflammation of the lower intestine with accumulation of thick yellow fluid. The bacterium enters the fish via the secondary gill lamellae and from there it spreads to the blood and internal organs. Y. ruckeri can be detected by conventional biochemical, serological and molecular methods. Its genome is 3.7 Mb with 3406–3530 coding sequences. Several important virulence factors of Y. ruckeri have been discovered, including haemolyin YhlA and metalloprotease Yrp1. Both non-specific and specific immune responses of fish during the course of Y. ruckeri infection have been well characterized. Several methods of vaccination have been developed for controlling both biotype 1 and biotype 2 Y. ruckeri strains in fish. This review summarizes the current state of knowledge regarding enteric redmouth disease and Y. ruckeri: diagnosis, genome, virulence factors, interaction with the host immune responses, and the development of vaccines against this pathogen.