Mycotoxins are a group of structurally diverse fungal secondary metabolites that elicit a wide spectrum of toxicological effects. Of particular interest is the capacity of some mycotoxins to alter normal immune function when present in food at levels below observable overt toxicity. The sensitivity of the immune system to mycotoxin-induced immunosuppression arises from the vulnerability of the continually proliferating and differentiating cells that participate in immune-mediated activities and regulate the complex communication network between cellular and humoral components. Mycotoxin-induced immunosuppression may be manifested as depressed T- or B-lymphocyte activity, suppressed antibody production and impaired macrophage/neutrophil-effector functions. The immune system is primarily responsible for defence against invading organisms. Suppressed immune function by mycotoxins may eventually decrease resistance to infectious diseases, reactivate chronic infections and/or decrease vaccine and drug efficacy.
Fumonisins constitute a family of toxic and carcinogenic mycotoxins produced by Fusarium verticillioides (formerly F. moniliforme), a common fungal contaminant of corn. Contamination with fumonisin B(1) (FB(1)) is of concern as this mycotoxin causes various animal diseases. The gastrointestinal tract represents the first barrier against ingested chemicals, food contaminants, and natural toxins. Following ingestion of fumonisin-contaminated food or feed, intestinal epithelial cells could be exposed to a high concentration of toxin. In this review, we have summarized the data dealing with the impact of FB(1) on the intestine. Although FB(1 )is poorly absorbed and metabolized in the intestine, it induces intestinal disturbances (abdominal pain or diarrhea) and causes extra-intestinal organ pathologies (pulmonary edema, leukoencephalomalacia, or neural tube defects). The main toxicological effect of FB(1) reported in vivo and in vitro is the accumulation of sphingoid bases associated with the depletion of complex sphingolipids. This disturbance of the sphingolipid biosynthesis pathway could explain the other observed toxicological effects such as an alteration in intestinal epithelial cell viability and proliferation, a modification of cytokine production, and a modulation of intestinal physical barrier function.
Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium verticillioides (formerly F. moniliforme), a fungus that commonly contaminates maize. FB1 causes toxicological effects in laboratory and domestic animals including pigs. Because the gastrointestinal tract represents the first barrier met by exogenous food compounds, the purpose of this study was to investigate the effects of FB1 on IPEC-1, a porcine intestinal epithelial cell line. We first verified that low concentrations of FB1 did not exert any cytotoxic effect on IPEC-1. Indeed, significant LDH release was only observed for FB1 concentrations greater than 50 and 700 microM on proliferating and nonproliferating cells, respectively. We then demonstrated that FB1 inhibits proliferation of IPEC-1. Fluorescence-activated cell sorting (FACS) analysis of the cell cycle indicated that FB1 blocks the proliferation of intestinal cells in the G0/G1 phase. Similar results were obtained with LLC-PK1, a renal porcine epithelial cell line, which is considered to be a good model for studying FB1 in vitro effects. We have also assessed the effects of FB1 on the integrity of the barrier formed by the intestinal epithelium. We demonstrated that FB1 decreases the transepithelial electrical resistance (TEER) of IPEC-1 in a time- and dose-dependent manner. This effect was only noticed after a long exposure (8-12 days of treatment). FB1 induced the TEER decrease independently of the cell differentiation stage, and this effect was partially reversible. Taken together, our data indicate that FB1 alters the proliferation and the barrier function of intestinal cells. These results may have implications for humans and animals consuming FB1-contaminated food or feed.
Fumonisin B1 (FB1), a mycotoxin produced by Fusarium verticillioides, may contaminate feed and food. In the present study, we investigated the effect of FB1 on the modulation of the cytokine profile and on the establishment of a vaccinal antibody response. In vitro investigations on pig peripheral blood mononuclear cells (PBMC) indicate that FB1 decreased interleukin-4 (IL-4) and increased interferon-gamma (IFN-gamma) synthesis at both the protein and mRNA levels. A short in vivo exposure (7 days) of weanling piglets to 1.5 mg/kg body weight of purified FB1 altered the cytokine balance in mesenteric lymph nodes and spleen similarly to the in vitro PBMC results. We also investigated the effect of FB1 on the antibody response during a vaccination process. A prolonged in vivo exposure (28 days) of weanling piglets to feed contaminated with 8 mg FB1/kg significantly decreased the expression of IL-4 mRNA by porcine whole blood cells and diminished the specific antibody titer after vaccination against Mycoplasma agalactiae. By contrast, ingestion of the contaminated feed had no effect on the serum concentration of the immunoglobulin subset (IgG, IgA, and IgM). Taken together, our data suggest that FB1 alters the cytokine profile and decreases the specific antibody response built during a vaccination protocol. These results may have implications for humans or animals eating contaminated food or feed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.