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Microalgae-based oral vaccines bolster aquaculture by sustainably enhancing fish immunity and curbing disease outbreaks. Here, we introduce the rational design of vaccine antigens and discuss the oral delivery and immune benefits of microalgae-based vaccines. We expect advances in synthetic biology and fish immune metabolism to drive microalgae-based vaccine innovation. Microalgae-based oral vaccines bolster aquaculture by sustainably enhancing fish immunity and curbing disease outbreaks. Here, we introduce the rational design of vaccine antigens and discuss the oral delivery and immune benefits of microalgae-based vaccines. We expect advances in synthetic biology and fish immune metabolism to drive microalgae-based vaccine innovation.

Cellular immune responses consist of innate and adaptive cell-mediated immune mechanisms, where all leukocyte subpopulations are included. Among these are vital processes such as cell-mediated cytotoxicity and phagocytosis. The main cellular constituents of the fish immune system are macrophages, granulocytes, dendritic cells, NK cells, and cytotoxic T cells. This review provides the latest information on cellular defense mechanisms of fish and provides an overview of the function of the mucosal immune system in maintaining the general health of fish. Here, we discuss the fundamental ideas that underpin mucosal immune responses in teleosts, as well as the innate and adaptive immune cells and the molecules that play a role in these immune responses. Moreover, cytokine molecules and pathways in teleosts have been reported to focus on several kinds of associated immunity. Importantly, we also review antigen processing and presentation. The knowledge reported here will enable better understanding, determination, and modulation of the pathways responsible for protective immunity, thus consequently improving the health of the fish in aquaculture.

There is a huge quantity of microorganisms in the gut of fish, which exert pivotal roles in maintaining host intestinal and general health. The fish immunity can sense and shape the intestinal microbiota and maintain the intestinal homeostasis. In the meantime, the intestinal commensal microbes regulate the fish immunity, control the extravagant proliferation of pathogenic microorganisms, and ensure the intestinal health of the host. This review summarizes developments and progress on the known interactions between host immunity and intestinal microorganisms in fish, focusing on the recent advances in zebrafish ( Danio rerio ) showing the host immunity senses and shapes intestinal microbiota, and intestinal microorganisms tune host immunity. This review will offer theoretical references for the development, application, and commercialization of intestinal functional microorganisms in fish. Key points • The interactions between the intestinal microorganisms and host immunity in zebrafish • Fish immunity senses and shapes the microbiota • Intestinal microbes tune host immunity in fish

Diseases are a significant impediment to aquaculture’s sustainable and healthy growth. The aquaculture industry is suffering significant financial losses as a result of the worsening water quality and increasing frequency of aquatic disease outbreaks caused by the expansion of aquaculture. Drug control, immunoprophylaxis, ecologically integrated control, etc. are the principal control strategies for fish infections. For a long time, the prevention and control of aquatic diseases have mainly relied on the use of various antibiotics and chemical drugs. However, long-term use of chemical inputs not only increases pathogenic bacteria resistance but also damages the fish and aquaculture environments, resulting in drug residues in aquatic products, severely impeding the development of the aquaculture industry. The development and use of aquatic vaccines are the safest and most effective ways to prevent aquatic animal diseases and preserve the health and sustainability of aquaculture. To give references for the development and implementation of aquatic vaccines, this study reviews the development history, types, inoculation techniques, mechanisms of action, development prospects, and challenges encountered with aquatic vaccines.

Melanomacrophage centers (MMCs) are aggregates of highly pigmented phagocytes found primarily in the head kidney and spleen, and occasionally the liver of many vertebrates. Preliminary histological analyses suggested that MMCs are structurally similar to the mammalian germinal center (GC), leading to the hypothesis that the MMC plays a role in the humoral adaptive immune response. For this reason, MMCs are frequently described in the literature as \"primitive GCs\" or the \"evolutionary precursors\" to the mammalian GC. However, we argue that this designation may be premature, having been pieced together from mainly descriptive studies in numerous distinct species. This review provides a comprehensive overview of the MMC literature, including a phylogenetic analysis of MMC distribution across vertebrate species. Here, we discuss the current understanding of the MMCs function in immunity and lingering questions. We suggest additional experiments needed to confirm that MMCs serve a GC-like role in fish immunity. Finally, we address the utility of the MMC as a broadly applicable histological indicator of the fish (as well as amphibian and reptilian) immune response in both laboratory and wild populations of both model and non-model vertebrates. We highlight the factors (sex, pollution exposure, stress, stocking density, etc.) that should be considered when using MMCs to study immunity in non-model vertebrates in wild populations.

Fish gut microbiota play important roles in fish immunity, nutrition, and the adaptation to environmental changes. To date, few studies have focused on the interactions among environmental factors, fish diseases, and gut microbiota compositions. We compared the gut bacterial communities of healthy crucian carps (Carassius auratus) with those of individuals affected by “red-operculum” disease and corresponding water and sediment microbiota in four fish farm ponds. Distinct gut bacterial communities were observed in healthy and diseased fish. The bacterial communities of diseased fish were less diverse and stable than those of healthy individuals. The differences in bacterial community compositions between diseased and healthy fish were explained by the changes in the relative abundances of some specific bacterial OTUs, which belonged to the genera such as Vibrio, Aeromonas, and Shewanella, and they were prevalent in diseased fish, but rare or even absent in environmental samples. Water temperature and ammonia concentration were the two most important environmental factors that impacted gut microbiota in diseased fish. These results highlighted the surge of some potential pathogens as bacterial signatures that were associated with “red-operculum” disease in crucian carps.

Teleost fish possess a highly diverse innate immune system, which is well-adapted to the pathogen-rich aquatic environment in which they reside. NOD-like receptors (NLRs), a conserved family of cytosolic pattern recognition receptors, are at the center of this defense mechanism, activating immune responses, recognizing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Here, we present an integrative overview of the current state of fish NLRs in terms of their evolutionary diversification, structural framework, signaling pathways, and functional roles in the context of bacterial, viral, and parasitic pathogens. We discuss six principal NLRs: nucleotide-binding oligomerization domain-containing protein 1 (NOD1), NOD2, NLRC3, NLRC5, NLR family member X1 (NLRX1), and NLR family pyrin domain-containing 1 (NLRP1), highlighting their domain structures, 3D conformations, and downstream signal chains. We focused on the immune regulatory roles of NLR family acidic transactivation domain-containing (NLRA) and NLR family CARD domain-containing (NLRC) subfamily components, the formation of the NLRP1 inflammasome, and the new roles of mitochondrial-specific NLRs in antiviral immunity. We discuss future directions for NLRs as immunological targets in aquaculture, referencing known NLR-activating adjuvants, exploring their ligand specificity, and highlighting challenges like functional redundancy. Much of the insight into the fish NLRs in this review comes from their well-researched mammalian counterparts. NLR-based immune modulation represents the ability of these receptors to detect microbial or danger signals and regulate key signaling pathways, such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), activator protein 1 (AP-1), interferon regulatory factors (IRFs), and inflammasome activation. These pathways help shape the immune response by negatively or positively altering cytokine production and improving antigen presentation. By bringing together what we know about NLR evolution, structure, and function, this review aims to support new ideas and research into how fish defend themselves from disease and how we might strengthen that defense through improved vaccine and adjuvant design.

In aquaculture studies, Spirulina can be used to replace fish meal in aquafeed to lower the cost of producing fish feed while adding therapeutic and health benefits. Proteins, carbohydrates, vitamins, minerals, pigments, and fatty acids from Spirulina could enhance the cellular and humoral immunities of a variety of fish species. This review focuses on the functions of various Spirulina components that play a role in haematopoiesis, haemato-biochemical variables, pro-inflammatory and anti-inflammatory cytokine production, stress prevention, disease resistance, and immune responses in a variety of finfish species. Herein, we also presented the overlooked areas on the functionality of Spirulina on the immune response pathway and connected the missing link with the help of a better knowledge of the mammalian system, albeit these must be proved experimentally. This review will inspire the scientific community to investigate the biological role of Spirulina in fish, which is critical to the commercial viability of Spirulina as fish feed.

Antimicrobial peptides (AMPs) are found widespread in nature and possess antimicrobial and immunomodulatory activities. Due to their multifunctional properties, these peptides are a focus of growing body of interest and have been characterized in several fish species. Due to their similarities in amino-acid composition and amphipathic design, it has been suggested that neuropeptides may be directly involved in the innate immune response against pathogen intruders. In this review, we report the molecular characterization of the fish-specific AMP piscidin1, the production of an antibody raised against this peptide and the immunohistochemical identification of this peptide and enkephalins in the neuroepithelial cells (NECs) in the gill of several teleost fish species living in different habitats. In spite of the abundant literature on Piscidin1, the biological role of this peptide in fish visceral organs remains poorly explored, as well as the role of the neuropeptides in neuroimmune interaction in fish. The NECs, by their role as sensors of hypoxia changes in the external environments, in combination with their endocrine nature and secretion of immunomodulatory substances would influence various types of immune cells that contain piscidin, such as mast cells and eosinophils, both showing interaction with the nervous system. The discovery of piscidins in the gill and skin, their diversity and their role in the regulation of immune response will lead to better selection of these immunomodulatory molecules as drug targets to retain antimicrobial barrier function and for aquaculture therapy in the future.

Serotonin (5-hydroxytryptamine) is a well-known neurotransmitter affecting emotion, behavior, and cognition. Additionally, numerous immunomodulatory functions of serotonin have been discovered in mammals. However, the regulatory role of the serotonin system in fish immunity remains unclear. In this study, various serotonergic markers in Nile tilapia ( Oreochromis niloticus ) were identified and characterized. The involvement of the serotonin system during bacterial infection was investigated. Moreover, the expression characteristics and specific functions of serotonergic markers within Nile tilapia immune cells were also assessed. Overall, 22 evolutionarily conserved serotonergic marker genes in Nile tilapia were cloned and characterized. Transcriptional levels of these molecules were most abundant in the brain, and their transcripts were induced during Streptococcus agalactiae infection. Nevertheless, few serotonergic markers exist on Nile tilapia immune cells, and no distinct immunomodulation effect was observed during an immune response. The present study lays a theoretical foundation for further investigation of the immunological mechanisms in fish as well as the evolution of the serotonin system in animals.