Effet chez le porcelet d'une exposition à un régime co-contaminé en ...

TRAVAIL EXPERIMENTALassociated lymphoid tissue (GALT) and act as inductive sites for intestinal immune response. Thesespecific tissues can be considered as specialized meeting places, where antigen-presenting cells andlymphocytes interact in presence of intestinal antigen. We investigated cytokines expression, whichare important mediators in the regulation of the immune and inflammatory responses. They areproduced by immune system cells (lymphocytes, macrophages, …) but also by cells not traditionallyconsidered as part of the immune system such as intestinal epithelial cells.Few data are available with regard to the effects of FB1 on the intestinal immunity, and evenlesser on cytokines production. FB1 decreases the expression and the synthesis of IL-8 in the porcineepithelial intestinal cell line, IPEC-1 (Bouhet et al., 2006). The same study confirmed this result invivo; ingestion of low doses of FB1 by piglets decreased the expression of IL-8 mRNA in the ileum.The FB1-induced IL-8 decrease may lead to a reduced recruitment of inflammatory cells in theintestine during infection and may participate in the observed increased susceptibility ofcontaminated piglets to intestinal infections (Oswald et al., 2003). Recently, another study showed inpiglets that following FB1 exposure, animals revealed a reduced intestinal expression of IL-12p40, animpaired function of intestinal antigen presenting cells (APC), with decreased upregulation of majorhistocompatibility complex class II molecule (MHC-II) and reduced T cell stimulatory capacity uponstimulation (Devriendt et al., 2009). As outlined by the authors, these results indicate an FB1-mediated reduction of in vivo APC maturation. In the current study, for most of the cytokinesinvestigated, we observed after FB1 ingestion a significant decrease of their expression in all thecompartments of the intestinal tract. By contrast, the profile of cytokines after exposition to HFB1revealed very few changes, close to the one observed in non-treated animals. These observationsimply that animals consuming HFB1 would be able to defend efficiently against potential invaders. Toour knowledge, this is the first study on the effects of HFB1 on some key components of theintestinal immune system.By contrast to FB1, the lack of effects, either at the hepatic or intestinal levels, observed followingHFB1 treatment might be explained by its ability to unaffect the sphingoid bases content. Indeed,FB1 acts as an inhibitor of the ceramide synthase, leading to an accumulation of sphinganine and to alesser extent of sphingosine. The establishment of the Sa/So ratio has been widely described to be arelevant and sensible biomarker of FB1 toxicity (Soriano et al., 2005, Tran et al., 2006), and illustratesthe degree of sphingolipid metabolism disruption. This elevation in sphinganine, a highly bioactivecompound, initiates a cascade of cellular alterations that are thought to be largely responsible for thetoxicity and carcinogenicity of this mycotoxin. To inhibit the ceramide synthase, aminopentolbackbone of FB1 competes for binding of the sphingoid base substrate, whereas the tricarballylicacids side chains (TCA) interfere with binding of the fatty acyl-CoA (Humpf et al., 1998; Desai et al.,139