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Mycotoxins, Immunity, and Inflammation
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Mycotoxins, Immunity, and Inflammation

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: 20 September 2025 | Viewed by 6563

Special Issue Editor

Prof. Dr. Yuseok Moon

E-Mail Website
Guest Editor
Laboratory of Mucosal Exposome and Biomodulation, Department of Integrative Biomedical Sciences, Biomedical Research Institute, Pusan National University, Yangsan 50612, Republic of Korea
Interests: immunotoxicity; mycotoxin; intestine; ribosome; mucosal immunology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This is a continue issue of our hot topic “Mycotoxins, Immunity, and Inflammation 2022”.

Toxic fungal components or metabolites, including mycotoxins, that are exposed to humans and animals, lead to detrimental effects on health and are closely associated with acute and chronic diseases. Among the targets of biological systems, the immune system is frequently affected and mediates the process of homeostasis and pathogenesis including inflammation. The immune system, including immune cells and cytokines, plays a pivotal role in modulating immune responses and inflammation during the disease process. Recent advances have greatly increased our understanding of mycotoxicoses in association with immune systems in health and immune-related pathogenesis of inflammation, infection, sepsis, tumor, immunosuppression, metabolic diseases, autoimmune disorders, degenerative diseases, and other diseases. Moreover, many mycotoxins interfering with homeostatic immune regulation may lead to immune suppression or cause excessive immune responses to autoantigens and hypersensitivity. We invite authors to submit original research articles and literature reviews that define the actions of toxic fungal components or metabolites including mycotoxins in immunological networks and the associated disease outcomes of exposure in humans and animals.

Prof. Dr. Yuseok Moon
Guest Editor

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Keywords

  • mycotoxin
  • immunity
  • inflammation
  • immunotoxicity
  • immunology

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Published Papers (5 papers)

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Research

18 pages, 823 KiB  
Article
The Initial Detection of Mycotoxins Released and Accumulated in the Golden Jackal (Canis aureus): Investigating the Potential of Carnivores as Environmental Bioindicators
by Péter Fehér, Zsófia Molnár, Mihály Péter Pálfi, Anikó Pálfiné Lábadi, Patrik Plank, István Lakatos, Miklós Heltai, László Szemethy, Viktor Stéger and Zsuzsanna Szőke
Int. J. Mol. Sci. 2025, 26(8), 3755; https://doi.org/10.3390/ijms26083755 - 16 Apr 2025
Viewed by 897
Abstract
This study investigated the presence and levels of five key mycotoxins—aflatoxins (AFs), deoxynivalenol (DON), fumonisin B1 (FB1), ochratoxin-A (OTA), and zearalenone (ZEN) and its metabolite alpha-zearalenol (α-ZOL)—in liver samples from 19 golden jackals (Canis aureus) in southern Hungary. Golden jackals, as [...] Read more.
This study investigated the presence and levels of five key mycotoxins—aflatoxins (AFs), deoxynivalenol (DON), fumonisin B1 (FB1), ochratoxin-A (OTA), and zearalenone (ZEN) and its metabolite alpha-zearalenol (α-ZOL)—in liver samples from 19 golden jackals (Canis aureus) in southern Hungary. Golden jackals, as apex predators with a diverse diet encompassing both plant and animal matter, can serve as valuable bioindicators of environmental mycotoxin contamination. Genetic analysis confirmed the canid samples as coming from golden jackals, excluding the possibility of domestic dogs or hybrid individuals. All samples tested positive for at least three mycotoxins, with multiple mycotoxins frequently co-occurring. DON was detected in 95% of the samples, followed by FB1 (79%) and ZEN (42%). ZOL, AFs, and OTA were present in all samples. Significant differences in mycotoxin concentrations were observed between age groups and sexes for some mycotoxins. Specifically, adult males exhibited higher ZEN concentrations, adult females had higher OTA levels, and females generally showed significantly higher DON concentrations than males. For all investigated individuals, we found significantly higher concentrations of ZEN, alpha-ZOL, and OTA in adult samples. Malondialdehyde (MDA), an indicator of oxidative stress, was also measured and correlated with mycotoxin levels. Pareto analysis suggested a correlation between MDA and OTA/ZEN. These findings highlight the exposure of golden jackals to a range of mycotoxins in their natural environments, potentially through both plant and animal food sources, and underscore the potential of these canids as sentinels for mycotoxin contamination in ecosystems. Full article
(This article belongs to the Special Issue Mycotoxins, Immunity, and Inflammation)
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24 pages, 8173 KiB  
Article
Microbial Guardians or Foes? Metagenomics Reveal Association of Gut Microbiota in Intestinal Toxicity Caused by DON in Mice
by Yujing Cui, Haoyue Guan, Samuel Kumi Okyere, Zixuan Hua, Youtian Deng, Huidan Deng, Zhihua Ren and Junliang Deng
Int. J. Mol. Sci. 2025, 26(4), 1712; https://doi.org/10.3390/ijms26041712 - 17 Feb 2025
Viewed by 504
Abstract
The role of gut microbiota has become a research hotspot in recent years; however, whether the gut microbiota are involved in the alleviation or exacerbation of Deoxynivalenol (DON) toxicity has not been fully studied. Therefore, the objective of this study was to investigate [...] Read more.
The role of gut microbiota has become a research hotspot in recent years; however, whether the gut microbiota are involved in the alleviation or exacerbation of Deoxynivalenol (DON) toxicity has not been fully studied. Therefore, the objective of this study was to investigate whether the gut microbiota are involved in reducing or aggravating the intestinal damage induced by DON in mice. Mice that received or did not receive antibiotic-induced intestinal flora clearance were orally given DON (5 mg kg/bw/day) for 14 days. At the end of the experiment, serum, intestinal tissue samples and colon contents were collected for further analysis. DON caused development of severe histopathological damage, such as necrosis and inflammation of the jejunum and colon in mice without gut microbiota clearance. The levels of tight junction proteins ZO-1 and occludin were reduced in the jejunum and colon of mice without gut microbiota clearance. In addition, the mRNA and protein levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) were increased in mice without gut microbiota clearance. The presence of microbiota exacerbate the intestinal damage induced by DON via changes in gut microbiota abundance and production of gut damaging metabolites. Full article
(This article belongs to the Special Issue Mycotoxins, Immunity, and Inflammation)
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19 pages, 3020 KiB  
Article
Leveraging Xenobiotic-Responsive Cancer Stemness in Cell Line-Based Tumoroids for Evaluating Chemoresistance: A Proof-of-Concept Study on Environmental Susceptibility
by Ki-Hyung Kim, Seung Joon Lee, Juil Kim and Yuseok Moon
Int. J. Mol. Sci. 2024, 25(21), 11383; https://doi.org/10.3390/ijms252111383 - 23 Oct 2024
Viewed by 1194
Abstract
Emerging evidence suggests that cancer stemness plays a crucial role in tumor progression, metastasis, and chemoresistance. Upon exposure to internal or external stress, ribosomes stand sentinel and facilitate diverse biological processes, including oncological responses. In the present study, ribosome-inactivating stress (RIS) was evaluated [...] Read more.
Emerging evidence suggests that cancer stemness plays a crucial role in tumor progression, metastasis, and chemoresistance. Upon exposure to internal or external stress, ribosomes stand sentinel and facilitate diverse biological processes, including oncological responses. In the present study, ribosome-inactivating stress (RIS) was evaluated for its modulation of cancer cell stemness as a pivotal factor of tumor cell reprogramming. Based on the concept of stress-responsive cancer cell stemness, we addressed human intestinal cancer cell line-based off-the-shelf spheroid cultures. Intestinal cancer cell line-based spheroids exhibited heightened levels of CD44+CD133+ cancer stemness, which was improved by chemical-induced RIS. Further evaluations revealed the potential of these stress-imprinted spheroids as a platform for chemoresistance screening. Compared to adherent cells, stemness-improved spheroid cultures displayed reduced apoptosis in response to 5-fluorouracil (5-FU), a frontline chemotherapeutic agent against colorectal cancer. Moreover, serial subcultures with repeated RIS exposure maintained and even enhanced cancer stemness and chemoresistance patterns. In particular, isolated CD44+CD133+ cancer stem cells exhibited higher chemoresistance compared to unsorted cells. To elucidate the mechanisms underlying RIS-induced stemness, RNA-seq analysis identified Wnt signaling pathways and stemness-associated signals as notable features in spheroids exposed to RIS. Loss-of-function studies targeting connective tissue growth factor (CTGF), a negative regulator of Wnt signaling, revealed that CTGF-deficient spheroids exhibited improved cancer stemness and resistance to 5-FU, with RIS further enhancing these effects. In conclusion, this proof-of-concept study demonstrates the feasibility of leveraging stress-responsive cancer stemness for the development of spheroid-based platforms for chemoresistance evaluation and elucidation of pathophysiological processes of colorectal tumorigenesis under environmental stress. Full article
(This article belongs to the Special Issue Mycotoxins, Immunity, and Inflammation)
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11 pages, 3104 KiB  
Article
Deoxynivalenol Induces Local Inflammation and Lesions in Tissues at Doses Recommended by the EU
by Alix Pierron, Luciana C. Balbo, Laura Soler, Philippe Pinton, Sylvie Puel, Joëlle Laffitte, Mickaël Albin, Ana-Paula F. R. Loureiro Bracarense, Maria A. Rodriguez and Isabelle P. Oswald
Int. J. Mol. Sci. 2024, 25(18), 9790; https://doi.org/10.3390/ijms25189790 - 10 Sep 2024
Cited by 1 | Viewed by 1068
Abstract
The mycotoxin deoxynivalenol (DON) is frequently present in cereals at low levels, resulting in its occurrence in food and feed. DON has been proven to alter the immune response and induce inflammation in all species, with pigs exhibiting heightened sensitivity and exposure. However, [...] Read more.
The mycotoxin deoxynivalenol (DON) is frequently present in cereals at low levels, resulting in its occurrence in food and feed. DON has been proven to alter the immune response and induce inflammation in all species, with pigs exhibiting heightened sensitivity and exposure. However, no study has yet evaluated the effects of exposure to DON at the recommended levels in pig feed. In two separate trials, piglets were subjected to control feed or feed contaminated with a low level of purified DON (0.83 mg/kg feed in trial 1 and 0.85 mg/kg feed in trial 2) for either three weeks (trial 1) or two weeks (trial 2). Additionally, a group of animals exposed to 2.85 mg/kg feed of DON was included as a positive control in Trial 1. The impact of DON on porcine tissues (intestine, liver, and spleen) was evaluated through histological and qPCR analyses of immune-related genes. Additionally, biochemical analyses and acute-phase proteins were examined in plasma samples. Lesions were identified in the intestine (jejunum and ileum), the liver, and the spleen of pigs receiving diets contaminated with low and high concentrations of DON. The low level of DON also resulted in impaired expression of genes associated with intestinal barrier integrity, intestinal immune responses, and liver function. In conclusion, the results of the two trials demonstrate the impact of DON exposure even at doses below the recommended level of 0.9 mg/kg feed set by the European Union. This suggests that the current recommended level should be reconsidered to ensure the optimal health and well-being of pigs. Full article
(This article belongs to the Special Issue Mycotoxins, Immunity, and Inflammation)
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12 pages, 2270 KiB  
Article
A Sensitive, Cell-Based Assay for Measuring Low-Level Biological Activity of α-Amanitin
by Reuven Rasooly, Paula Do, Xiaohua He and Bradley Hernlem
Int. J. Mol. Sci. 2023, 24(22), 16402; https://doi.org/10.3390/ijms242216402 - 16 Nov 2023
Cited by 1 | Viewed by 1840
Abstract
α-Amanitin is one of the primary toxins produced by the poisonous mushroom genus, Amanita. Because it is odorless and tasteless, it is an important cause of death from the consumption of misidentified mushrooms. To study the thermal stability of α-amanitin, novel cell-based [...] Read more.
α-Amanitin is one of the primary toxins produced by the poisonous mushroom genus, Amanita. Because it is odorless and tasteless, it is an important cause of death from the consumption of misidentified mushrooms. To study the thermal stability of α-amanitin, novel cell-based assays were developed to measure the toxin’s activity, based on the inhibition of RNA polymerase II by α-amanitin. First, an MTT–formazan cell viability assay was used to measure the biological activity of α-amanitin through the inhibition of cellular activity. This method can detect 10 μg/mL of α-amanitin in a time-dependent manner. Second, a more sensitive quantitative PCR approach was developed to examine its inhibition of viral replication. The new RT-qPCR assay enabled the detection of 100 ng/mL. At this level, α-amanitin still significantly reduced adenovirus transcription. Third, a simpler GFP expression-based assay was developed with an equal sensitivity to the RT-qPCR assay. With this assay, aqueous α-amanitin heated at 90 °C for 16 h or treated in the microwave for 3 min retained its biological activity when tested in HEK293 cells, but a slight reduction was observed when tested in Vero cells. Beyond detecting the activity of α-amanitin, the new method has a potential application for detecting the activity of other toxins that are RNA polymerase inhibitors. Full article
(This article belongs to the Special Issue Mycotoxins, Immunity, and Inflammation)
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