Introduction
Toxicity induced by mycotoxins on the immune system is known as immunotoxicity, and it encompasses their adverse effects on both local and systemic immune responses. The severity and nature of these effects depend on several factors, such as the type of mycotoxin, the dose and duration of exposure, the species, sex, and certain immunological stimulants (Sun et al., 2023). In addition, aspects related to genetics, nutritional status and interaction with other toxic compounds also intervene (Oliveira & Vasconcelos, 2020).
Traditionally, the effect of mycotoxins on the immune system has been considered primarily immunosuppressive, leading to a greater susceptibility to infections and reduced efficacy of vaccination programs. However, there is growing evidence of their immunostimulatory capacity and how they can alter inflammatory responses, thereby also compromising animal health (Sun et al., 2022; Pestka, 2010).
Effects of mycotoxins on the immune system of aquatic species
In aquatic species, mycotoxins exert immunotoxic effects through multiple interrelated mechanisms that compromise animal health and survival. These toxins induce oxidative stress, increasing the production of reactive oxygen species (ROS) and reducing the activity of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT), which causes generalized cell damage and alters immune function (Abdel-Tawwab et al., 2021; Chen et al., 2020). Specifically, the T-2 toxin can decrease CAT gene expression, impairing antioxidant function (Yu et al., 2023). Ochratoxin (OTA), deoxynivalenol (DON), T-2 toxin, and fumonisin B1 (FB1) can affect lipid peroxidation, where DON and OTA elevate early-phase markers (conjugated dienes and trienes) and FB1 increases the termination marker (malondialdehyde, MDA) (Kövesi et al., 2020). Exposure to the T-2 toxin also causes a significant increase in lipid peroxidation in the liver and caudal kidney of the common carp (Cyprinus carpio) (Matejova et al., 2017).
Furthermore, mycotoxins modulate the gene expression of key cytokines and transcription factors, such as TNF-α, IL-1β, IL-4, NF-κB, and the Toll/IMD pathways, affecting the communication and coordination of the immune response (Su et al., 2023; Abdel-Tawwab et al., 2021). For example, the T-2 toxin and DON, by inhibiting the synthesis of proteins, DNA, and RNA, can affect the immune system (Kövesi et al., 2020).
At cellular level, mycotoxins induce apoptosis and necrosis of lymphocytes, hemocytes, and macrophages in aquatic species, decreasing the number of immunocompetent cells and weakening the defenses against pathogens (Qiu et al., 2016; Mexía-Salazar et al., 2008). The T-2 toxin induces apoptosis through oxidative stress, activating the mitochondrial pathways (Kövesi et al., 2020). In the Chinese mitten crab (Eriocheir sinensis), the T-2 toxin promotes apoptosis, evidenced by the upregulation of the Caspase gene and the downregulation of the apoptosis inhibitor BIRC2 (Yu et al., 2023).
Mycotoxins also compromise the integrity of mucosal barriers and essential immune organs, such as the hepatopancreas, reducing their ability to maintain an effective immune barrier (Wang et al., 2018; Huang et al., 2019; Pérez-Acosta et al., 2016). Chronic exposure to OTA in channel catfish (Ictalurus punctatus) leads to an increased incidence and severity of melanomacrophage centers (MMCs) in the hepatopancreatic tissue and posterior kidney, and a reduction in the exocrine pancreatic cells surrounding the hepatic portal veins (Manning et al., 2003). In crustaceans, aflatoxin B1 (AFB1) causes significant histopathological alterations, primarily in the hepatopancreas, such as atrophy, necrosis, and hemocyte infiltration (Ghaednia et al., 2013). The T-2 toxin in the Chinese mitten crab (E. sinensis) also causes significant damage to the hepatopancreas, which triggers protective autophagy, evidenced by the upregulation of ATG4 and PERK (Yu et al., 2023). Furthermore, AFB1 can induce the upregulation of genes related to antibacterial function and detoxification in the hepatopancreas of the Chinese mitten crab (E. sinensis), such as the anti-lipopolysaccharide factor (Yang et al., 2023).
Mycotoxicosis and susceptibility to infectious diseases in aquaculture
Despite the fact that, due to the complexity of the immune system, there are still many aspects to clarify regarding the interaction of mycotoxins and immune function, it is currently known that exposure to these contaminants can increase the severity of infection caused by some pathogens, including bacteria, viruses, and parasites (Sun et al., 2023). Specifically, it has been reported that exposure to mycotoxins can directly promote the proliferation of pathogenic microorganisms; increase their toxicity, through the alteration of mucosal barrier integrity and the promotion of the inflammatory response; and reduce the activity of some specific immune cells, inducing immunosuppression and thereby compromising host resistance (Sun et al., 2023).
The immunosuppressive effect of mycotoxins in aquatic species and, consequently, their reduced resistance to certain pathogens, has been reported in different in vivo studies. Yu et al. (2025) reported a decreased immune response of European seabass (Dicentrarchus labrax) against the pathogenic bacterium Vibrio alginolyticus after being exposed to zearalenone (ZEN) for 4 weeks. This study recorded lower production of white blood cells, serum proteins, albumin, globulin, and lysozyme, as well as increased mortality after infection. ZEN has been shown to have strong estrogenic activity in vivo, inducing, for example, an increase in plasma vitellogenin (VTG) in male zebrafish (Danio rerio), which indicates an endocrine disruption relevant to immune function (Schwartz et al., 2010).
Sherif and Zommara (2024) reported immunosuppression in Nile tilapia (Oreochromis niloticus) exposed to AFB1. In this case, exposure to the mycotoxin for 8 weeks resulted in lower serum antibacterial activity, oxidative burst activity, phagocytosis, and cytokine expression (IL-1β, Hsp70 y TNF-α), increasing the animals’ vulnerability to Streptococcus agalactiae, and triggering high mortality. In the same species, FB1 exposure can reduce disease resistance (Tuan et al., 2003). AFB1 also decreased the natural resistance of indian white shrimp (Fenneropenaeus indicus) to pathogens (Ghaednia et al., 2013).
Again, a study conducted on striped catfish (Pangasianodon hypophthalmus) exposed to AFB1 at low doses of 50 to 250 μg/kg of feed, reported lower natural resistance to the bacterium Edwardsiella ictaluri, one of the most important pathogens in this species (Gonçalves et al., 2018). Similarly, OTA and FB1 in the diet reduce disease resistance in channel catfish (I. punctatus) (Lumlertdacha and Lovell, 1995; Kövesi et al., 2020).
Dietary T-2 toxin has been shown to suppress growth and induce immunotoxicity in the Chinese mitten crab (E. sinensis) (Wang et al., 2020b). Additionally, T-2 toxin in common carp (C. carpio) induced anemia (decrease in hematocrit, hemoglobin, and red blood cells) and leukopenia (decrease in white blood cells), and caused changes in the non-specific immune response and cytokine levels in the head kidney (Matejova et al., 2017).
Finally, Xue et al. (2023) studied the immune response of gibel carp (Carassius gibelio) exposed to AFB1 against cyprinid herpesvirus 2 (CyHV-2). The assay showed reduced resistance to the virus in the exposed animals, with increased mortality and viral load, due to oxidative stress, reduction of antioxidant enzymes, and suppression of immune genes, in addition to alterations in the gut microbiota.
Conclusion
Based on the review of the results provided by various studies, the necessity of implementing mycotoxin mitigation strategies in aquaculture is reaffirmed. Moreover, the lack of research on other high-value aquatic species is highlighted. Contributing to the development of preventive and corrective measures in this field is essential for preserving the immunocompetence of the animals, thereby maintaining their productivity, ensuring the sustainability and safety of aquaculture systems.
