T-2 toxin inhibits the differentiation of human monocytes into dendritic cells and macrophages
ABSTRACT 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.
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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 · 2.58 Impact Factor
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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 · 2.38 Impact Factor
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ABSTRACT: Group I CD1 (CD1a, CD1b, and CD1c) glycoproteins expressed on immature and mature dendritic cells present nonpeptide antigens (i.e., lipid or glycolipid molecules mainly of microbial origin) to T cells. Cytotoxic CD1-restricted T lymphocytes recognizing mycobacterial lipid antigens were found in tuberculosis patients. However, thanks to a complex interplay between mycobacteria and CD1 system, M. tuberculosis possesses a successful tactic based, at least in part, on CD1 downregulation to evade CD1-dependent immunity. On the ground of these findings, it is reasonable to hypothesize that modulation of CD1 protein expression by chemical, biological, or infectious agents could influence host's immune reactivity against M. tuberculosis-associated lipids, possibly affecting antitubercular resistance. This scenario prompted us to perform a detailed analysis of the literature concerning the effect of external agents on Group I CD1 expression in order to obtain valuable information on the possible strategies to be adopted for driving properly CD1-dependent immune functions in human pathology and in particular, in human tuberculosis.Clinical and Developmental Immunology 03/2011; 2011:790460. DOI:10.1155/2011/790460 · 2.93 Impact Factor