The effects of mycotoxins, fungal food contaminants, on the intestinal epithelial cell-derived innate immune response

Abstract

Mycotoxins are structurally diverse fungal metabolites that can contaminate a variety of dietary components consumed by animals and humans. It is considered that 25% of the world crop production is contaminated by mycotoxins. The clinical toxicological syndromes caused by ingestion of moderate to high amounts of mycotoxins and their effect on the immune system have been well characterized. However, no particular attention has been focused on the effects of mycotoxins on the local intestinal immune response. Because of their location, intestinal epithelial cells (IECs) could be exposed to high doses of mycotoxins. As a component of the innate local immune response, intestinal epithelial cells have developed a variety of mechanisms which act to reduce the risk of infection by microorganisms or intoxication by toxic compounds. This review summarises the innate immune response developed by intestinal epithelial cells and reports the literature concerning the effects of mycotoxins on them. Particularly, the effects of mycotoxins on the maintenance of a physical barrier by epithelial cells will be discussed together with their effect on extrinsic protective components of the innate intestinal immunity: mucus secretion, antimicrobial peptide generation, IgA and pro-inflammatory cytokine release.

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).