T-2 toxin inhibits the differentiation of human monocytes into dendritic cells and macrophages
Food Toxicology Laboratory, EA 3880, UFR Sciences et Techniques, 6 avenue Le Gorgeu-CS 93837-29238 Brest cedex 3, Brest University, France. Toxicology in Vitro
(Impact Factor: 2.9).
05/2009; 23(3):509-19. DOI: 10.1016/j.tiv.2009.01.003
The aim of this work was to study the in vitro effect of T-2 toxin on human monocyte differentiation into macrophages and dendritic cells. Cytotoxicity of T-2 toxin on monocytes, on monocytes in differentiation process into macrophages or dendritic cells, and on immature dendritic cells and macrophages was evaluated to determine IC50. Monocytes are more sensitive to T-2 toxin than to differentiate cells. IC50 were equal to 0.11 nM for monocyte, to 45 and 30 nM for monocyte during differentiation process for 24 and 48 h of incubation, respectively, to 38 and 20 nM for immature dendritic cells after 24 and 48 h of incubation, and to 22 and 20 nM for macrophages after 24 and 48 h of incubation. T-2 toxin effects on monocyte differentiation process into macrophages have been explored: according to phenotypic expressions (CD71, CD14, CD11a, CD80, CD86, HLA-DR and CD64), endocytic capacity, phagocytosis, burst respiratory activity and TNF-alpha secretion. In the presence of 10 nM of T-2 toxin (no cytotoxic concentration), CD71 expression is downregulated compared to control. Endocytosis and phagocytosis capacities are less effective as burst respiratory activity and TNF-alpha secretion. Monocyte differentiation process into dendritic cells in the presence of 10 nM T-2 toxin is also markedly disturbed. Expression of CD1a (specific dendritic cells marker) is downregulated while that of CD14 (specific monocyte marker) is upregulated. CD11a, CD80, CD86, HLA-DR and CD64 expressions did not change. These results show that T-2 toxin disturbs human monocytes differentiation process into macrophages and dendritic cells. These results could significantly contribute to immunosuppressive properties of this alimentary toxin.
Available from: Anne-Sophie Ficheux
- "de on mature murine dendritic cells ( Luongo et al . , 2010 ) . Exposure to T - 2 toxin during the differentiation of human monocytes in macrophages induced an inhibition of cell surface expression of CD71 , a decrease of endocytic activity , a diminution of production of reactive oxygen in - termediates and an inhibition of secretion of TNF - a ( Hymery et al . , 2009 ) . DON induced an inhibition of the expression of the cell surface receptors CD54 , CD14 , CD119 and HLA - DR on human macrophages stimulated with IFNg ( Waché et al . , 2009 ) . DON increased the secretion of in - flammatory cytokines TNFa and IL - 1b on LPS - stimulated porcine macrophages ( Döll et al . , 2009 ) . DON and nivale - n"
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ABSTRACT: The aim of this study was to assess the in vitro effects of emerging mycotoxins beauvericin, enniatin B and moniliformin on human dendritic cells and macrophages. Beauvericin and enniatin B were cytotoxic on these cells. IC50 were equal to 1.0 μM, 2.9 μM and 2.5 μM beauvericin for immature dendritic cells, mature dendritic cells and macrophages, respectively. IC50 were equal to 1.6 μM, 2.6 μM and 2.5 μM for immature dendritic cells, mature dendritic cells and macrophages exposed to enniatin B, respectively. Effects on the differentiation process of monocytes into macrophages or into immature dendritic cells as well as effects on dendritic cells maturation have been studied. The differentiation process of monocytes into immature dendritic cells was not disturbed in the presence of beauvericin. Dendritic cells exposed to beauvericin during the maturation process presented a decrease of CCR7 expression and an increase of IL-10 secretion. Monocytes exposed to beauvericin during the differentiation process into macrophages presented a decrease of endocytosis ability. The differentiation process of monocytes into immature dendritic cells was not disturbed in the presence of enniatin B. Dendritic cells exposed to enniatin B during the maturation process presented a decrease of expression of the maturation makers CD80, CD86 and CCR7 and an increase of IL-10 secretion. Monocytes exposed to enniatin B during the differentiation process into macrophages presented a decrease of endocytosis ability and an increase of CD71. CD1a expression and endocytosis capacity were decreased on immature dendritic cells exposed to moniliformin. Monocytes-derived macrophages exposed to moniliformin during the differentiation process presented a decrease of endocytosis ability, and a decrease of CD71 and HLA-DR expression. According to these results, immunological disorders could be observed on human after ingestion of these alimentary toxins.
Toxicon 05/2013; 71. DOI:10.1016/j.toxicon.2013.04.024 · 2.49 Impact Factor
Available from: Romain Solinhac
- "An exposure of T-2 toxin is associated with leucopenia and cell depletion in lymphoid organs and inhibition of erythropoiesis in bone marrow and the spleen . Furthermore, T-2 toxin reduces lymphocyte proliferative response [8,9] and disturbs the maturation process of dendritic cells  suggesting its immunosuppressant potency [7,11]. Indeed, it was previously shown that exposure to T-2 suppresses immune response to systemic infections by bacterial infection such as Salmonella typhimurium, Listeria monocytogenes, Mycobacterium bovis, Babesia microti. "
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ABSTRACT: 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.
Veterinary Research 04/2012; 43(1):35. DOI:10.1186/1297-9716-43-35 · 2.82 Impact Factor
Available from: HJ (Ine) Van der Fels-Klerx
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ABSTRACT: This paper presents an overview of the occurrence of T-2 toxin and HT-2 toxin in cereals in Europe and derived food products, factors influencing the occurrence, co-occurrence with other trichothecenes, and toxicological effects of T-2 and HT-2 in human. Of all cereals, oats showed to be most susceptible to T-2/HT-2 contamination. Particularly, oats grown in Scandinavia and UK in the period 2003-2007 were highly contaminated. This contamination has reduced in 2008 and 2009. In raw cereals, T-2 and HT-2 levels were highly correlated with each other in most instances, with the HT-2 level being two to seven times higher than the T-2 level. The toxin levels showed not to be correlated with levels of deoxynivalenol and nivalenol. The occurrence of T-2 and HT-2 in the field varied between years, regions, cereal grain varieties, sowing time, and precrop. Organically produced cereals contained lower T-2 and HT-2 levels as compared to conventionally grown cereals. Little or no effects from using fungicides was seen. Processing cereals resulted in low T-2 and HT-2 levels in food products, although oat products contained some T-2 and HT-2. The by-products from food processing, often used for animal feeding, frequently were highly contaminated. T-2 and HT-2 showed to have high acute and subacute toxicity, as they caused haematotoxic, immunotoxic, cytotoxic, and dermal effects. Carcinogenicity of T-2 and HT-2 in human has not been proven. Outbreaks of human toxicosis caused by trichothecenes, including T-2 and HT-2, have been reported. The present overview is deemed to be valuable for risk assessments at the European level, planned to be held by EFSA. It also provides directions for further research, including the ecology of the fungi responsible for T-2 and HT-2, and agronomical practices to reduce the contamination in the field.
World Mycotoxin Journal 11/2010; 3(4). DOI:10.3920/WMJ2010.1237 · 2.16 Impact Factor
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