Molecular Mechanisms of the Non-Specific Immunity of Fish When Responding to Pathogen Infections

A Special Issue of Fishes (ISSN 2410-3888) belonging to the section "Welfare, Health and Disease".

Deadline for manuscript submissions: 31 January 2027 | Viewed by 1643

Editors

College of Fisheries, Guangdong Ocean University, Zhanjiang 524003, China
Interests: aquatic fish diseases; fish immunology; immune regulatory mechanisms
College of Animal Science and Technology, Guangxi University, Nanning 530004, China
Interests: neuroimmunity in teleost; high-throughput sequencing; evolution of the immune system

Special Issue Information

Dear Colleagues,

Diseases caused by pathogens such as viruses and bacteria remain one of the most significant challenges restricting the sustainable development of global aquaculture. Although many studies have explored the immunology and innate defense strategies of fish, the molecular mechanism of how fish defend against early infections by pathogenic bacteria through non-specific immune responses is still not clear. This Special Issue, ‘Molecular Mechanisms of the Non-specific Immunity of Fish When Responding to Pathogen Infections’, aims to highlight the interactions between pathogens, hosts, and immune regulatory mechanisms. In particular, we will focus on the latest progress in non-specific immune defense strategies. We welcome studies on the immune responses of different immune cell populations to different pathogens, the receptors and signaling pathways of immune cell populations, pathogen-derived virulence factors, and the molecular immunology of infection. By integrating research from virology, bacteriology, and fish immunology, this Special Issue aims to fill key knowledge gaps and provide a deeper understanding of the role of non-specific immunity in fish during pathogen infections. 

Dr. Yu Huang
Dr. Qi Li
Guest Editors

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Keywords

  • teleost immunity
  • immune signaling pathways
  • viral and bacterial infections
  • virulence factors

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Published Papers (3 papers)

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Research

19 pages, 1820 KB  
Article
Assessment of the Probiotic Potential of Three Host-Associated Bacillus Species on Growth Performance, Health Status, and Immune Responses of Tomato Clownfish (Amphiprion frenatus)
by Qinyu Lv, Tao Li, Yan Liu, Dapeng Yu, Xinwei Jiang, Lixiong Chen and Jia Cai
Fishes 2026, 11(10), 582; https://doi.org/10.3390/fishes11100582 - 5 Oct 2026
Abstract
Antibiotic use in marine ornamental fish farming has raised concerns about resistance and tissue damage, motivating the search for safe probiotic alternatives. In this study, three Bacillus strains—B. subtilis (BS), B. megaterium (BM), and B. velezensis (BV)—that were isolated from healthy clownfish [...] Read more.
Antibiotic use in marine ornamental fish farming has raised concerns about resistance and tissue damage, motivating the search for safe probiotic alternatives. In this study, three Bacillus strains—B. subtilis (BS), B. megaterium (BM), and B. velezensis (BV)—that were isolated from healthy clownfish intestines were evaluated as dietary supplements for Amphiprion frenatus over a four-week feeding trial. The growth performance of the fish, the antioxidant enzyme activity in the liver and intestine, and the expression of pro-inflammatory and antimicrobial peptide genes in four tissues were examined. The intestinal barrier genes and intestinal morphology were also measured. The obtained data indicate that BM elicited the broadest immune activation, upregulated antimicrobial peptides and all four barrier genes, and increased the hepatosomatic index and MDA. BV has the best promotional effects on growth without elevating the hepatosomatic index; it selectively induced lyz and leap2 while suppressing gill il1b, and it reduced intestinal MDA. BS showed comparatively mild effects. These findings demonstrate strain-specific probiotic actions in clownfish, with B. velezensis offering the most favorable balance of growth promotion and immunomodulation for aquaculture applications. Full article
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19 pages, 10220 KB  
Article
Neuroimmune Interactions in the Intestine of Goldfish (Carassius auratus): Insights into Enteric Neurons and Immune Cell Organization
by Doaa M. Mokhtar, Eugenia Rita Lauriano, Marialuisa Aragona, Hailah M. Almohaimeed, Nashmiah S. Alshammari, Anthea Miller, Tahani A. Al-Matrafi, Maria Cristina Guerrera, Giorgia Pia Lombardo, Adriana Nunnari and Giacomo Zaccone
Fishes 2026, 11(6), 359; https://doi.org/10.3390/fishes11060359 - 16 Jun 2026
Cited by 1 | Viewed by 563
Abstract
Neuroimmune interactions in the intestine are essential for maintaining tissue homeostasis, yet they remain poorly understood in teleost fish. This study investigated the structural and cellular organization of enteric neurons and immune cells in the intestine of goldfish (Carassius auratus) using [...] Read more.
Neuroimmune interactions in the intestine are essential for maintaining tissue homeostasis, yet they remain poorly understood in teleost fish. This study investigated the structural and cellular organization of enteric neurons and immune cells in the intestine of goldfish (Carassius auratus) using semithin histology, transmission electron microscopy (TEM), and confocal immunofluorescence. Histological observations revealed a well-organized epithelium composed of enterocytes and goblet cells, with numerous lymphocytes located in the basal epithelium. Prominent gut-associated lymphoid tissue (GALT) was identified in both scattered and aggregated forms within the lamina propria and submucosa. Macrophages were widely distributed throughout all intestinal layers and were consistently found in close proximity to enteric neurons and nerve fibers. Ultrastructural analysis confirmed direct contacts between macrophages and neuronal elements. These macrophages exhibited typical phagocytic features, including lysosomes, vacuoles, and engulfed material, particularly in association with myenteric nerve fibers. Immunofluorescence analysis revealed strong expression of toll-like receptor 2 (TLR2) and major histocompatibility complex class II (MHC II) in macrophages and enterocytes, suggesting an active role in antigen recognition. Langerin-positive dendritic-like cells were identified in the submucosa, while CD4-positive lymphocytes showed partial colocalization with serotonin (5-HT). S100-positive cells also exhibited partial overlap with 5-HT, and goblet cells demonstrated serotonin immunoreactivity. In addition, inducible nitric oxide synthase (iNOS) colocalized with TLR2 in submucosal immune cells. These findings demonstrate a close structural and functional association between enteric neurons and immune cells, highlighting an integrated neuroimmune network in the goldfish intestine. Full article
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12 pages, 586 KB  
Article
In Vitro Analysis of the Tissue Distribution, Lifespan, and Antigen-Dependent Maintenance of Specific Antibody-Secreting Cells in Nile Tilapia
by Yu Huang, Zhe Cai, Bijian Pang, Zaohe Wu, Bei Wang, Jia Cai and Jichang Jian
Fishes 2026, 11(3), 184; https://doi.org/10.3390/fishes11030184 - 19 Mar 2026
Viewed by 494
Abstract
This study aimed to elucidate the key characteristics of the humoral immune response and the tissue distribution of specific antibody-secreting cells (ASCs) in Nile tilapia (Oreochromis niloticus). A specific immune model was established by immunizing fish with human IgG. Lymphocytes were [...] Read more.
This study aimed to elucidate the key characteristics of the humoral immune response and the tissue distribution of specific antibody-secreting cells (ASCs) in Nile tilapia (Oreochromis niloticus). A specific immune model was established by immunizing fish with human IgG. Lymphocytes were isolated from the head kidney, spleen, and peripheral blood and subjected to antigen stimulation in vitro. The MTT assay, reflecting cell metabolic activity and viability, identified the optimal culture conditions as a cell concentration of 2.5 × 106 cells/mL, an antigen concentration of 2 μg/mL, and a culture duration of 72 h. Under these conditions, peripheral blood lymphocytes exhibited the most increase in metabolic activity, followed by head kidney lymphocytes, while splenic lymphocytes showed no significant response. Subsequent dynamic monitoring of antibody-secreting cells (ASCs) using ELISPOT revealed that, in the absence of antigen stimulation, ASC numbers from all three tissues declined over time. Notably, head kidney ASCs retained approximately 50% of their initial number by day 5, whereas ASCs in peripheral blood and spleen decayed to barely detectable or completely undetectable levels, respectively. These findings suggest that the head kidney may serve as a primary site for ASC persistence during the effector phase, potentially contributing to sustained humoral immunity. Although antigen stimulation did not induce significant ASC expansion, it significantly slowed their decay rate (p < 0.05), indicating an antigen-dependent maintenance role. ELISA detection of antibody levels in the culture supernatants showed a consistent trend with the ELISPOT results, further confirming the sustained functional support of antigen for ASCs. Additionally, LPS stimulation experiments demonstrated that all three tissues contained plasmablasts activatable by non-specific stimuli, with peripheral blood showing the highest proliferation fold (4–6 times). In conclusion, this study provides insights into the tissue-specific distribution, in vitro persistence, and antigen-dependent maintenance of ASCs in Nile tilapia, providing insights into the cellular basis that may contribute to humoral immune memory and laying a theoretical foundation for the rational design and application of tilapia vaccines. Full article
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