The mycotoxin Deoxynivalenol inhibits the cell surface expression of activation markers in human macrophages

Waché, Yann; Hbabi-Haddioui, Laila; Guzylack‐Piriou, Laurence; Belkhelfa, Haouaria; Roques, Christine; Oswald, Isabelle P.

doi:10.1016/j.tox.2009.06.014

Cited by 32 publications

(15 citation statements)

References 34 publications

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“…The resulting increase of TNF-α production by DCs could trigger breakdown of the intestinal epithelium and facilitate bacterial translocation to the lamina propria , increasing risks of IBD [62]. It has already been demonstrated that DON alters the intestinal microbiota of pigs [63]. It thus comes as no surprise that in this study, exposure to DON could possibly lead to induction of colitogenic populations and to strong impairment of the epithelial barrier by the lack of effect on T-bet and significant increase of the expression levels of TNF-α.…”

Section: Discussionmentioning

confidence: 99%

Deoxynivalenol as a New Factor in the Persistence of Intestinal Inflammatory Diseases: An Emerging Hypothesis through Possible Modulation of Th17-Mediated Response

et al. 2013

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Background/AimsDeoxynivalenol (DON) is a mycotoxin produced by Fusarium species which is commonly found in temperate regions worldwide as a natural contaminant of cereals. It is of great concern not only in terms of economic losses but also in terms of animal and public health. The digestive tract is the first and main target of this food contaminant and it represents a major site of immune tolerance. A finely tuned cross-talk between the innate and the adaptive immune systems ensures the homeostatic equilibrium between the mucosal immune system and commensal microorganisms. The aim of this study was to analyze the impact of DON on the intestinal immune response.MethodologyNon-transformed intestinal porcine epithelial cells IPEC-1 and porcine jejunal explants were used to investigate the effect of DON on the intestinal immune response and the modulation of naive T cells differentiation. Transcriptomic proteomic and flow cytometry analysis were performed.Results DON induced a pro-inflammatory response with a significant increase of expression of mRNA encoding for IL-8, IL-1α and IL-1β, TNF-α in all used models. Additionally, DON significantly induced the expression of genes involved in the differentiation of Th17 cells (STAT3, IL–17A, IL-6, IL-1β) at the expenses of the pathway of regulatory T cells (Treg) (FoxP3, RALDH1). DON also induced genes related to the pathogenic Th17 cells subset such as IL–23A, IL-22 and IL-21 and not genes related to the regulatory Th17 cells (rTh17) such as TGF-β and IL-10.Conclusion DON triggered multiple immune modulatory effects which could be associated with an increased susceptibility to intestinal inflammatory diseases.

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Section: Discussionmentioning

confidence: 99%

Deoxynivalenol as a New Factor in the Persistence of Intestinal Inflammatory Diseases: An Emerging Hypothesis through Possible Modulation of Th17-Mediated Response

et al. 2013

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“…This alteration of lymphocyte proliferation might be due to an effect of these toxins on antigen-presenting cells (APC) as suggested by recent in vitro studies on monocytederived APC treated with DON [39,40] or in vivo studies with piglets acutely exposed to FB [27].…”

Section: Discussionmentioning

confidence: 99%

Individual and combined effects of subclinical doses of deoxynivalenol and fumonisins in piglets

Grenier

Bracarense

Lucioli

et al. 2011

Molecular Nutrition Food Res

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“…However, the effects of T-2 toxin seem to be TLR-receptor specific since neither co-receptor CD14 nor mannose receptor (CD206) were affected by the toxin. Our group has already shown in a previous study that DON can also inhibit cell surface expression of activation markers of human macrophages such as CD14, CD54, CD119 and HLA-DR [51]. …”

Section: Discussionmentioning

confidence: 99%

The fungal T-2 toxin alters the activation of primary macrophages induced by TLR-agonists resulting in a decrease of the inflammatory response in the pig

Seeboth

Solinhac

Oswald

et al. 2012

Vet Res

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T-2 toxin is known to be one of the most toxic trichothecene mycotoxins. Exposure to T-2 toxin induces many hematologic and immunotoxic disorders and is involved in immuno-modulation of the innate immune response. The objective of this work was to evaluate the effects of T-2 toxin on the activation of macrophages by different agonists of Toll-like receptors (TLR) using an in vitro model of primary porcine alveolar macrophages (PAM). Cytotoxic effects of T-2 toxin on PAM were first evaluated. An IC50 of 19.47 ± 0.9753 nM was determined for the cytotoxicity of T-2 toxin. A working concentration of 3 nM of T-2 toxin was chosen to test the effect of T-2 toxin on TLR activation; this dose was not cytotoxic and did not induce apoptosis as demonstrated by Annexin/PI staining. A pre-exposure of macrophages to 3 nM of T-2 toxin decreased the production of inflammatory mediators (IL-1 beta, TNF-alpha, nitric oxide) in response to LPS and FSL1, TLR4 and TLR2/6 agonists respectively. The decrease of the pro-inflammatory response is associated with a decrease of TLR mRNA expression. By contrast, the activation of TLR7 by ssRNA was not modulated by T-2 toxin pre-treatment. In conclusion, our results suggest that ingestion of low concentrations of T-2 toxin affects the TLR activation by decreasing pattern recognition of pathogens and thus interferes with initiation of inflammatory immune response against bacteria and viruses. Consequently, mycotoxins could increase the susceptibility of humans and animals to infectious diseases.

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The mycotoxin Deoxynivalenol inhibits the cell surface expression of activation markers in human macrophages

Cited by 32 publications

References 34 publications

Deoxynivalenol as a New Factor in the Persistence of Intestinal Inflammatory Diseases: An Emerging Hypothesis through Possible Modulation of Th17-Mediated Response

Deoxynivalenol as a New Factor in the Persistence of Intestinal Inflammatory Diseases: An Emerging Hypothesis through Possible Modulation of Th17-Mediated Response

Individual and combined effects of subclinical doses of deoxynivalenol and fumonisins in piglets

The fungal T-2 toxin alters the activation of primary macrophages induced by TLR-agonists resulting in a decrease of the inflammatory response in the pig

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