Comparative analysis of tropomyosin allergenicity in three different species of molluscs: insights into the role of amino acid composition in IgE epitopes.

Limited research has been conducted on the differences in allergenicity among Alectryonella plicatula tropomyosin (ATM), Haliotis discus hannai tropomyosin (HTM), and Mimachlamys nobilis tropomyosin (MTM) in molluscs. Our study aimed to comprehensively analyze and compare their immunoreactivity, sensitization, and allergenicity while simultaneously elucidating the underlying molecular mechanisms involved. We assessed the immune binding activity of TM utilizing 86 sera from allergic patients and evaluated sensitization and allergenicity through two different types of mouse models. The dot-blot and basophil activation test assays revealed strong immunoreactivity for HTM, ATM, and MTM, with HTM exhibiting significantly lower levels compared to ATM. In the BALB/c mouse sensitization model, all TM groups stimulated the production of specific antibodies, elicited IgE-mediated immediate hypersensitivity responses, and caused an imbalance in the IL-4/IFN-γ ratio. Similarly, in the BALB/c mouse model of food allergy, all TM variants induced IgE-mediated type I hypersensitivity responses, leading to the development of food allergies characterized by clinical symptoms and an imbalance in the IL-4/IFN-γ ratio. The stimulation ability of sensitization and the severity of food allergies consistently ranked as ATM > MTM > HTM. Through an in-depth analysis of non-polar amino acid frequency and polar hydrogen bonds, HTM exhibited higher frequencies of non-polar amino acids in its amino acid sequence and IgE epitopes, in comparison with ATM and MTM. Furthermore, HTM demonstrated a lower number of polar hydrogen bonds in IgE epitopes. Overall, HTM exhibited the lowest allergenic potential in both allergic patients and mouse models, likely due to its lower polarity in the amino acid sequence and IgE epitopes.

Identification of peptidoglycan recognition proteins in hemocytes and kidney of common periwinkle Littorinalittorea.

Peptidoglycan Recognition Proteins (PGRPs) are a diverse group of proteins involved in innate immunity. In particular, PGRPs have been shown to participate in immune pattern recognition in various mollusks. However, they have not been described in Caenogastropoda, a large molluscan group comprising sea, freshwater and land snails. In this study, four short PGRPs with molecular weights ranging from 21 to 34 kDa and their isoforms were identified and structurally characterized in the kidney and hemocytic transcriptomes of a caenogastropod mollusk Littorina littorea. All of them (LlPGRP1-4) are secretory, possess a signal peptide and a characteristic N-terminal N-acetylmuramoyl-l-alanine amidase (Ami) domain with conserved Zn2+ binding- and amidase catalytic sites. The shortest proteins, LlPGRP1 and LlPGRP2, have no additional conserved motifs on the N-terminus. In longer and most abundantly expressed LlPGRP3 and LlPGRP4 the Ami-domain is combined with an N-terminal SH3-domain and a cysteine-rich motif, respectively. Expression analysis showed that LlPGRPs of the common periwinkle were uninvolved in the immune response to infection with trematode Himasthla elongata though they might act in antibacterial defense.

Susceptibility of Four Abalone Species, Haliotis gigantea, Haliotis discus discus, Haliotis discus hannai and Haliotis diversicolor, to Abalone asfa-like Virus.

Abalone amyotrophia is a viral disease that causes mass mortality of juvenile Haliotis discus and H. madaka. Although the cause of this disease has yet to be identified, we had previously postulated a novel virus with partial genome sequence similarity to that of African swine fever virus is the causative agent and proposed abalone asfa-like virus (AbALV) as a provisional name. In this study, three species of juvenile abalone (H. gigantea, H. discus discus, and H. diversicolor) and four species of adult abalone (the above three species plus H. discus hannai) were experimentally infected, and their susceptibility to AbALV was investigated by recording mortality, quantitatively determining viral load by PCR, and conducting immunohistological studies. In the infection test using 7-month-old animals, H. gigantea, which was previously reported to be insusceptible to the disease, showed multiplication of the virus to the same extent as in H. discus discus, resulting in mass mortality. H. discus discus at 7 months old showed abnormal cell masses, notches in the edge of the shell and brown pigmentation inside of the shell, which are histopathological and external features of this disease, while H. gigantea did not show any of these characteristics despite suffering high mortality. Adult abalones had low mortality and viral replication in all species; however, all three species, except H. diversicolor, became carriers of the virus. In immunohistological observations, cells positive for viral antigens were detected predominantly in the gills of juvenile H. discus discus and H. gigantea, and mass mortality was observed in these species. In H. diversicolor, neither juvenile nor adult mortality from infection occurred, and the AbALV genome was not increased by experimental infection through cohabitation or injection. Our results suggest that H. gigantea, H. discus discus and H. discus hannai are susceptible to AbALV, while H. diversicolor is not. These results confirmed that AbALV is the etiological agent of abalone amyotrophia.

The primitive interferon-like system and its antiviral function in molluscs.

The phylum mollusca is a very important group in the animal kingdom for the large number and diversified species. Recently, interest in molluscan immunity has increased due to their phylogenetic position and importance in worldwide aquaculture and aquatic environment. As the main aquaculture animal, most molluscs live in the water environment and they have to cope with many pathogen challenges, in which virus is one of the primary causes for the mass mortality. In vertebrates, interferon (IFN) system is generally recognized as the first line of defence against viral infection, while the antiviral mechanisms in molluscs remain to be clearly illuminated. Recently, some IFN-like proteins and IFN-related components have been characterized from molluscs, such as pattern recognition receptors (PRRs), interferon regulatory factors (IRFs), IFN-like receptors, JAK/STAT and IFN-stimulated genes (ISGs), which reinforce the existence of IFN-like system in molluscs. This system can be activated by virus or poly (I:C) challenges and further regulate the antiviral response of haemocytes in molluscs. This review summarizes the research progresses of IFN-like system in molluscs with the emphases on the uniformity and heterogeneity of IFN-like system of molluscs compared to that of other animals, which will be helpful for elucidating the antiviral modulation in molluscs and understanding the origin and evolution of IFN system.

Applications of flow cytometry in molluscan immunology: Current status and trends.

Flow cytometry (FCM) is routinely used in fundamental and applied research, clinical practice, and clinical trials. In the last three decades, this technique has also become a routine tool used in immunological studies of molluscs to analyse physical and chemical characteristics of haemocytes. Here, we briefly review the current implementation of FCM in the field of molluscan immunology. These applications cover a diverse range of practices from straightforward total cell counts and cell viability to characterize cell subpopulations, and further extend to analyses of DNA content, phagocytosis, oxidative stress and apoptosis. The challenges and prospects of FCM applications in immunological studies of molluscs are also discussed.

TLR4, but Neither Dectin-1 nor Dectin-2, Participates in the Mollusk Hemocyanin-Induced Proinflammatory Effects in Antigen-Presenting Cells From Mammals.

Mollusk hemocyanins have biomedical uses as carriers/adjuvants and nonspecific immunostimulants with beneficial clinical outcomes by triggering the production of proinflammatory cytokines in antigen-presenting cells (APCs) and driving immune responses toward type 1 T helper (Th1) polarization. Significant structural features of hemocyanins as a model antigen are their glycosylation patterns. Indeed, hemocyanins have a multivalent nature as highly mannosylated antigens. We have previously shown that hemocyanins are internalized by APCs through receptor-mediated endocytosis with proteins that contain C-type lectin domains, such as mannose receptor (MR). However, the contribution of other innate immune receptors to the proinflammatory signaling pathway triggered by hemocyanins is unknown. Thus, we studied the roles of Dectin-1, Dectin-2, and Toll-like receptor 4 (TLR4) in the hemocyanin activation of murine APCs, both in dendritic cells (DCs) and macrophages, using hemocyanins from Megathura crenulata (KLH), Concholepas concholepas (CCH) and Fissurella latimarginata (FLH). The results showed that these hemocyanins bound to chimeric Dectin-1 and Dectin-2 receptors in vitro; which significantly decreased when the glycoproteins were deglycosylated. However, hemocyanin-induced proinflammatory effects in APCs from Dectin-1 knock-out (KO) and Dectin-2 KO mice were independent of both receptors. Moreover, when wild-type APCs were cultured in the presence of hemocyanins, phosphorylation of Syk kinase was not detected. We further showed that KLH and FLH induced ERK1/2 phosphorylation, a key event involved in the TLR signaling pathway. We confirmed a glycan-dependent binding of hemocyanins to chimeric TLR4 in vitro. Moreover, DCs from mice deficient for MyD88-adapter-like (Mal), a downstream adapter molecule of TLR4, were partially activated by FLH, suggesting a role of the TLR pathway in hemocyanin recognition to activate APCs. The participation of TLR4 was confirmed through a decrease in IL-12p40 and IL-6 secretion induced by FLH when a TLR4 blocking antibody was used; a reduction was also observed in DCs from C3H/HeJ mice, a mouse strain with a nonfunctional mutation for this receptor. Moreover, IL-6 secretion induced by FLH was abolished in macrophages deficient for TLR4. Our data showed the involvement of TLR4 in the hemocyanin-mediated proinflammatory response in APCs, which could cooperate with MR in innate immune recognition of these glycoproteins.

A review on the application of Bacillus as probiotics in aquaculture.

Probiotics use in aquaculture has gained attention as microbial candidates to maintain the health and the well-being of many aquaculture animals. Among the many microbial candidates, probiotic Bacillus has sporulation capacity that makes them survive harsh environmental conditions, are non-pathogenic and non-toxic when fed to fish, and can produce antimicrobial substances making them more suitable candidates compared to other probiotics. In this review, we discussed the necessity of using the probiotic Bacillus in sustainable aquaculture as a good alternative to improve feed utilization, stress response, immune response and disease resistance, maintenance of tissue integrity, and as well improvement of water quality for sustainable aquaculture. Therefore the findings of current researches about the effects of Bacillus application to improve the culture of aquatic animals for future research and development of Bacillus application in aquaculture have been summarised.

Open questions: knowing who's who in multicellular animals is not always as simple as we imagine.

The ability of certain tumor cells of mammals and molluscs to spread from the original host to others reopens the question of distinguishing self from non-self. It is part of a wider phenomenon of cellular parasitism and cell chimerism including germ cells.

Metagenomic sequencing suggests a diversity of RNA interference-like responses to viruses across multicellular eukaryotes.

RNA interference (RNAi)-related pathways target viruses and transposable element (TE) transcripts in plants, fungi, and ecdysozoans (nematodes and arthropods), giving protection against infection and transmission. In each case, this produces abundant TE and virus-derived 20-30nt small RNAs, which provide a characteristic signature of RNAi-mediated defence. The broad phylogenetic distribution of the Argonaute and Dicer-family genes that mediate these pathways suggests that defensive RNAi is ancient, and probably shared by most animal (metazoan) phyla. Indeed, while vertebrates had been thought an exception, it has recently been argued that mammals also possess an antiviral RNAi pathway, although its immunological relevance is currently uncertain and the viral small RNAs (viRNAs) are not easily detectable. Here we use a metagenomic approach to test for the presence of viRNAs in five species from divergent animal phyla (Porifera, Cnidaria, Echinodermata, Mollusca, and Annelida), and in a brown alga-which represents an independent origin of multicellularity from plants, fungi, and animals. We use metagenomic RNA sequencing to identify around 80 virus-like contigs in these lineages, and small RNA sequencing to identify viRNAs derived from those viruses. We identified 21U small RNAs derived from an RNA virus in the brown alga, reminiscent of plant and fungal viRNAs, despite the deep divergence between these lineages. However, contrary to our expectations, we were unable to identify canonical (i.e. Drosophila- or nematode-like) viRNAs in any of the animals, despite the widespread presence of abundant micro-RNAs, and somatic transposon-derived piwi-interacting RNAs. We did identify a distinctive group of small RNAs derived from RNA viruses in the mollusc. However, unlike ecdysozoan viRNAs, these had a piRNA-like length distribution but lacked key signatures of piRNA biogenesis. We also identified primary piRNAs derived from putatively endogenous copies of DNA viruses in the cnidarian and the echinoderm, and an endogenous RNA virus in the mollusc. The absence of canonical virus-derived small RNAs from our samples may suggest that the majority of animal phyla lack an antiviral RNAi response. Alternatively, these phyla could possess an antiviral RNAi response resembling that reported for vertebrates, with cryptic viRNAs not detectable through simple metagenomic sequencing of wild-type individuals. In either case, our findings show that the antiviral RNAi responses of arthropods and nematodes, which are highly divergent from each other and from that of plants and fungi, are also highly diverged from the most likely ancestral metazoan state.

Pathogen-Derived Carbohydrate Recognition in Molluscs Immune Defense.

Self-nonself discrimination is a common theme for all of the organisms in different evolutionary branches, which is also the most fundamental step for host immune protection. Plenty of pattern recognition receptors (PRRs) with great diversity have been identified from different organisms to recognize various pathogen-associated molecular patterns (PAMPs) in the last two decades, depicting a complicated scene of host-pathogen interaction. However, the detailed mechanism of the complicate PAMPs-PRRs interactions at the contacting interface between pathogens and hosts is still not well understood. All of the cells are coated by glycosylation complex and thick carbohydrates layer. The different polysaccharides in extracellular matrix of pathogen-host are important for nonself recognition of most organisms. Coincidentally, massive expansion of PRRs, majority of which contain recognition domains of Ig, leucine-rich repeat (LRR), C-type lectin (CTL), C1q and scavenger receptor (SR), have been annotated and identified in invertebrates by screening the available genomic sequence. The phylum Mollusca is one of the largest groups in the animal kingdom with abundant biodiversity providing plenty of solutions about pathogen recognition and immune protection, which might offer a suitable model to figure out the common rules of immune recognition mechanism. The present review summarizes the diverse PRRs and common elements of various PAMPs, especially focusing on the structural and functional characteristics of canonical carbohydrate recognition proteins and some novel proteins functioning in molluscan immune defense system, with the objective to provide new ideas about the immune recognition mechanisms.

Evolutionary Origins of Toll-like Receptor Signaling.

Toll-like receptors (TLRs) are transmembrane pattern recognition receptors that are best known for their roles in innate immunity for the detection of and defense against microbial pathogens. However, TLRs also have roles in many nonimmune processes, most notably development. TLRs direct both immune and developmental programs by activation of downstream signaling pathways, often by activation of the NF-κB pathway. There are two primary TLR subtypes: 1) TLRs with multiple cysteine clusters in their ectodomain (mccTLRs) and 2) TLRs with a single cysteine cluster in their ectodomain (sccTLRs). For some time, it has been known that TLRs and the biological processes that they control are conserved in organisms from insects to mammals. However, genome and transcriptome sequencing has revealed that many basal metazoans also have TLRs and downstream NF-κB signaling components. In this review, we discuss what is known about the structure, biological function, and downstream signaling pathways of TLRs found in phyla from Porifera through Annelida. From these analyses, we hypothesize that mccTLRs emerged in the phylum Cnidaria, that sccTLRs evolved in the phylum Mollusca, and that TLRs have dual immune and developmental biological functions in organisms as ancient as cnidarians.

Comparative immunogenomics of molluscs.

Comparative immunology, studying both vertebrates and invertebrates, provided the earliest descriptions of phagocytosis as a general immune mechanism. However, the large scale of animal diversity challenges all-inclusive investigations and the field of immunology has developed by mostly emphasizing study of a few vertebrate species. In addressing the lack of comprehensive understanding of animal immunity, especially that of invertebrates, comparative immunology helps toward management of invertebrates that are food sources, agricultural pests, pathogens, or transmit diseases, and helps interpret the evolution of animal immunity. Initial studies showed that the Mollusca (second largest animal phylum), and invertebrates in general, possess innate defenses but lack the lymphocytic immune system that characterizes vertebrate immunology. Recognizing the reality of both common and taxon-specific immune features, and applying up-to-date cell and molecular research capabilities, in-depth studies of a select number of bivalve and gastropod species continue to reveal novel aspects of molluscan immunity. The genomics era heralded a new stage of comparative immunology; large-scale efforts yielded an initial set of full molluscan genome sequences that is available for analyses of full complements of immune genes and regulatory sequences. Next-generation sequencing (NGS), due to lower cost and effort required, allows individual researchers to generate large sequence datasets for growing numbers of molluscs. RNAseq provides expression profiles that enable discovery of immune genes and genome sequences reveal distribution and diversity of immune factors across molluscan phylogeny. Although computational de novo sequence assembly will benefit from continued development and automated annotation may require some experimental validation, NGS is a powerful tool for comparative immunology, especially increasing coverage of the extensive molluscan diversity. To date, immunogenomics revealed new levels of complexity of molluscan defense by indicating sequence heterogeneity in individual snails and bivalves, and members of expanded immune gene families are expressed differentially to generate pathogen-specific defense responses.

Cross-talk among immune and neuroendocrine systems in molluscs and other invertebrate models.

The comparison between immune and neuroendocrine systems in vertebrates and invertebrates suggest an ancient origin and a high degree of conservation for the mechanisms underlying the integration between immune and stress responses. This suggests that in both vertebrates and invertebrates the stress response involves the integrated network of soluble mediators (e.g., neurotransmitters, hormones and cytokines) and cell functions (e.g., chemotaxis and phagocytosis), that interact with a common objective, i.e., the maintenance of body homeostasis. During evolution, several changes observed in the stress response of more complex taxa could be the result of new roles of ancestral molecules, such as ancient immune mediators may have been recruited as neurotransmitters and hormones, or vice versa. We review older and recent evidence suggesting that immune and neuro-endocrine functions during the stress response were deeply intertwined already at the dawn of multicellular organisms. These observations found relevant reflections in the demonstration that immune cells can transdifferentiate in olfactory neurons in crayfish and the recently re-proposed neural transdifferentiation in humans.

Seafood-Associated Shellfish Allergy: A Comprehensive Review.

Shellfish are diverse, serve as main constituents of seafood, and are extensively consumed globally because of their nutritional values. Consequently, increase in reports of IgE-mediated seafood allergy is particularly food associated to shellfish. Seafood-associated shellfish consists of crustaceans (decapods, stomatopods, barnacles, and euphausiids) and molluskans (gastropods, bivalves, and cephalopods) and its products can start from mild local symptoms and lead to severe systemic anaphylactic reactions through ingestion, inhalation, or contact like most other food allergens. Globally, the most commonly causative shellfish are shrimps, crabs, lobsters, clams, oysters, and mussels. The prevalence of shellfish allergy is estimated to be 0.5-2.5% of the general population but higher in coastal Asian countries where shellfish constitute a large proportion of the diet. Diversity in allergens such as tropomyosin, arginine kinase, myosin light chain, and sarcoplasmic binding protein are from crustaceans whereas tropomyosin, paramyosin, troponin, actine, amylase, and hemoyanin are reported from molluskans shellfish. Tropomyosin is the major allergen and is responsible for cross-reactivity between shellfish and other invertebrates, within crustaceans, within molluskans, between crustaceans vs. molluskans as well as between shellfish and fish. Allergenicity diagnosis requires clinical history, in vivo skin prick testing, in vitro quantification of IgE, immunoCAP, and confirmation by oral challenge testing unless the reactions borne by it are life-threatening. This comprehensive review provides the update and new findings in the area of shellfish allergy including demographic, diversity of allergens, allergenicity, their cross-reactivity, and innovative molecular genetics approaches in diagnosing and managing this life-threatening as well as life-long disease.

A molluscan calreticulin ortholog from Haliotis discus discus: Molecular characterization and transcriptional evidence for its role in host immunity.

Calreticulin (CALR), a Ca(2+) binding chaperone of the endoplasmic reticulum (ER) and mainly involved in Ca(2+) storage and signaling. In this study, we report the molecular characterization and immune responses of CALR homolog from disk abalone (AbCALR). The full length AbCALR cDNA (1837 bp) had an ORF of 1224 bp. According to the multiple alignments analysis, N- and P-domains were highly conserved in all the selected members of CALRs. In contrast, the C-domain which terminated with the characteristic ER retrieval signal (HDEL) was relatively less conserved. The phylogenetic analysis showed that all the selected molluscan homologs clustered together. Genomic sequence of AbCALR revealed that cDNA sequence was dispersed into ten exons interconnected with nine introns. AbCALR mRNA expression shows the significant (P < 0.05) up-regulation of AbCALR transcripts in hemocytes upon bacterial (Listeria monocytogenes and Vibrio parahaemolyticus), viral (Viral haemorrhagic septicaemia virus; VHSV) and immune stimulants (LPS and poly I:C) challenges at middle and/or late phases. These results collectively implied that AbCALR is able to be stimulated by pathogenic signals and might play a potential role in host immunity.

Infectious diseases of marine molluscs and host responses as revealed by genomic tools.

More and more infectious diseases affect marine molluscs. Some diseases have impacted commercial species including MSX and Dermo of the eastern oyster, QPX of hard clams, withering syndrome of abalone and ostreid herpesvirus 1 (OsHV-1) infections of many molluscs. Although the exact transmission mechanisms are not well understood, human activities and associated environmental changes often correlate with increased disease prevalence. For instance, hatcheries and large-scale aquaculture create high host densities, which, along with increasing ocean temperature, might have contributed to OsHV-1 epizootics in scallops and oysters. A key to understanding linkages between the environment and disease is to understand how the environment affects the host immune system. Although we might be tempted to downplay the role of immunity in invertebrates, recent advances in genomics have provided insights into host and parasite genomes and revealed surprisingly sophisticated innate immune systems in molluscs. All major innate immune pathways are found in molluscs with many immune receptors, regulators and effectors expanded. The expanded gene families provide great diversity and complexity in innate immune response, which may be key to mollusc's defence against diverse pathogens in the absence of adaptive immunity. Further advances in host and parasite genomics should improve our understanding of genetic variation in parasite virulence and host disease resistance.

Antiviral immunity in marine molluscs.

Marine molluscs, like all living organisms, are constantly exposed to viruses and have evolved efficient antiviral defences. We review here recent developments in molluscan antiviral immunity against viruses belonging to the order Herpesvirales. Emerging results suggest an interferon-like response and autophagy are involved in the antiviral defence of bivalves to viral infection. Multi-functional plasma proteins from gastropods and bivalves have been identified to have broad-spectrum antiviral activity against mammalian viruses. The antiviral defences present in molluscs can be enhanced by genetic selection, as shown by the presence of oyster strains specifically resistant to ostreid herpesvirus type 1. Whether varying amounts or different isoforms of these antiviral plasma proteins contributes to genetic resistance is worthy of further research. Other evolutionarily conserved antiviral mechanisms, such as RNA interference and apoptosis, still need further characterization.

[REACTION OF HAEMOCYTES OF THE MOLLUSK PLANORBARIUS CORNEUS TO A XENOTRANSPLANT].

Tissue reaction of the mollusk Planorbarius corneus to the introduction of a transplant (cat vibrissa) was examined. The transplant was introduced into mollusk tissues with the use of an injection needle. After a day, flattened haemocytes were found on the surface of the transplant. The wound channel formed by the needle was arrested by a capsule formed of 5-15 layers of flattened cells. The cavity of the wound channel and the core of the vibrissa were also filled with haemocytes. During incubation of the vibrissa in vitro, adhesion and sedimentation of haemocytes on its surface was observed.

Sensitization pattern of crustacean-allergic individuals can indicate allergy to molluscs.

This study investigated the sensitization pattern of crustacean-allergic patients according to tolerance to molluscs. Thirty-one patients with anaphylaxis to crustaceans (14 with mollusc allergy and 17 with mollusc tolerance) were studied using skin prick tests (SPTs), specific IgEs (sIgEs) and SDS-PAGE immunoblotting. IgE-reactive shrimp proteins were identified by proteomic analyses. Patients with mollusc allergy presented more frequently SPTs positive to molluscs and higher sIgE titres in response to both molluscs and crustaceans. Shrimp-sIgE and rPen a1-sIgE values of 1.57 kUA /l and 4.38 kUA /l, respectively, showed positive likelihood ratios of 4.3 and 10.9 for the identification of mollusc allergy. Patients with mollusc allergy reacted more frequently to tropomyosin in immunoblots than did patients without it (93% vs 35%, respectively, P = 0.004). Reactivity to proteins other than tropomyosin (n = 14) was not different between the two groups. Among patients with crustacean anaphylaxis, patients with mollusc allergy and mollusc tolerance show a different pattern of sensitization, something that may help identify them.

Probiotics and prebiotics associated with aquaculture: A review.

There is a rapidly growing literature, indicating success of probiotics and prebiotics in immunomodulation, namely the stimulation of innate, cellular and humoral immune response. Probiotics are considered to be living microorganisms administered orally and lead to health benefits. These Probiotics are microorganisms in sufficient amount to alter the microflora (by implantation or colonization) in specific host's compartment exerting beneficial health effects at this host. Nevertheless, Prebiotics are indigestible fiber which enhances beneficial commensally gut bacteria resulting in improved health of the host. The beneficial effects of prebiotics are due to by-products derived from the fermentation of intestinal commensal bacteria. Among the many health benefits attributed to probiotics and prebiotics, the modulation of the immune system is one of the most anticipated benefits and their ability to stimulate systemic and local immunity, deserves attention. They directly enhance the innate immune response, including the activation of phagocytosis, activation of neutrophils, activation of the alternative complement system, an increase in lysozyme activity, and so on. Prebiotics acting as immunosaccharides directly impact on the innate immune system of fish and shellfish. Therefore, both probiotics and prebiotics influence the immunomodulatory activity boosting up the health benefits in aquatic animals.