The effects of mycotoxins, fungal food contaminants, on the intestinal epithelial cell-derived innate immune response
Introduction
Mycotoxins are structurally diverse low-molecular-weight metabolites produced by fungi. As secondary metabolites they are not essential to fungal growth and are produced sporadically under fungal stress. Mycotoxins can be produced during both culture and storage. They can contaminate a variety of feed and food consumed by animals and humans; essentially cereals, but also fruits, grains, forages, and manufactured products (Table 1). Most mycotoxins in feed and food are produced by three genera of fungi: Aspergillus, Penicillium, and Fusarium (Table 1). These toxins account annually for millions of dollars in losses worldwide, in condemned agricultural products and in animal and human health (CAST, 2003). Due to their toxic properties and their high stability to heat treatment, the presence of mycotoxins in the food chain is potentially hazardous to the health of both humans and animals. The clinical toxicological syndromes caused by ingestion of moderate to high amounts of mycotoxins have been well characterized. They range from acute mortality, to slowed growth and reduced reproductive efficiency. Consumption of lesser amounts of fungal toxins may result in impaired immunity (Corrier, 1991). Several papers have detailed the effects of mycotoxins on the immune response in domestic and laboratory animals (Bondy and Pestka, 2000, Corrier, 1991, Oswald and Coméra, 1998) but the effect of mycotoxins on the intestinal local immune response has not been reviewed.
Following ingestion of contaminated food or feed, the intestine and the intestinal epithelial cell layer could be exposed to a high concentration of food contaminant such as mycotoxins (Prelusky et al., 1996, Shephard et al., 1995). The intestinal layer is the first barrier preventing the entry of foreign antigens, including food proteins, natural toxins, commensal gut flora and pathogens, into the underlying tissues. This barrier function is based both on innate and adaptive components of immunity. Recent data have detailed the involvement of intestinal epithelial cells (IECs) in these local immune responses (Eckmann et al., 1995, Pitman and Blumberg, 2000, Shao et al., 2001). A primary function of these cells is to act as a physical barrier, separating the contents of a harsh luminal environment from the layers of tissue comprising the internal milieu. As a consequence of their exposed location, IECs have developed a variety of mechanisms besides the maintenance of barrier function, which act to reduce the risk of infection by invasive foreign agents. Such mechanisms include those which act directly to inhibit bacterial colonization along the exposed surface of the monolayer (protective mucus and antimicrobial peptide secretion) and those which function through an interactive process with cells of the underlying immune organization (IgA and pro-inflammatory cytokine synthesis). This review attempts to summarise the effects of food contaminants, especially mycotoxins, on the local immune response developed by IECs (Fig. 1).
Section snippets
The epithelial barrier and its inter-cellular junctions
Epithelial integrity is critical in maintaining a physical but selective barrier between external and internal environments. This barrier function is maintained by well-organized intercellular structures including tight junctions, adherence junctions and desmosomes surrounding the apical region of epithelial cells (Gumbiner, 1993). The trans-epithelial electrical resistance (TEER) of cell monolayers can be considered as a good indicator of the epithelial integrity and of the degree of
The mucus protective layer
The mucus barrier is composed of mucins associated with other proteins and lipids. It forms a continuous gel into which a bicarbonate-rich fluid is secreted, maintaining a neutralizing pH at the epithelial surface. Mucins are usually subdivided into two groups: the membrane-anchored (gel-forming) and the secreted mucins (non gel-forming) (Desseyn et al., 2000). They are synthesized and secreted by goblet cells through baseline secretion and an active exocytosis (Perez-Vilar and Hill, 1999). The
Conclusion
The intestinal mucosa is the first barrier encountered by natural toxins, consequently it could be exposed to high amounts of dietary toxins. Because of their ability to associate into a protective epithelium and to release protective molecules, intestinal epithelial cells are active components of the local innate immunity. The present review describes several mycotoxins that disrupt the intrinsic barrier function of intestinal epithelial cells by altering the epithelial integrity and impairing
Acknowledgements
We are grateful to Dr. Neil Ledger for helpful comments regarding the manuscript. Sandrine Bouhet was supported by a Fellowship from the Ministère de l’Education Nationale, de la Recherche et de la Technologie. This work was supported in part by the Région Midi-Pyrénées, France (DAER-Rech/99008345) and by the Transversalité INRA (Mycotoxines-P00263).
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