Mycotoxins, which are toxic secondary metabolites produced by molds, are potentially harmful to human and animal health upon consumption of mycotoxin-contaminated food or feed. The contamination of agricultural products by mycotoxin-producing molds remains a serious concern for animal and human health. Despite monitoring programs and many specific regulations, humans and animals could still be exposed to mycotoxins, present at low levels in feed and food. Among these mycotoxins, aflatoxins (AFs), especially AFB1, are the most toxic and carcinogenic to mammals. Further, AFB1 impairs cell-mediated immunity, though the exact mechanism of this immunotoxicity is not well-known. By far the most pivotal cells in the induction of immune responses are dendritic cells (DCs). These highly specialized cells dictate T-cell activation/polarisation depending on the nature of the encountered antigens and environmental cues. To elucidate the effect of AFB1 on the key molecules and the function of DCs, we used human monocyte-derived DCs (MDDCs) as a model system and performed cell culture, qPCR and flow cytometry assays. An environmentally relevant level of AFB1 remarkably impaired the phagocytic capacity of MDDCs. Furthermore, as compared to untreated MDDCs, AFB1 significantly affected on the transcription of some key functional genes in MDDCs, i.e., upregulated mRNA expression of key cytochrome P450 (CYP) families, MyD88, NF-KB, TNF-a, TLR2, TLR4, COX-2, HLA, CD16, and downregulated mRNA expression of AhR, TGF-b, CD11c and CD64 at 2-12 h post treatment. In contrast, the transcription of some other key genes, e.g., IL-10, IL-1b, AKR7A2, GSTM1, IL-6. IL-8, C5aR, CCR7, CD209 and LFA3 in post-AFB1 treated MDDCs only slightly changed. Our results in this study indicate that an environmentally relevant level of AFB1 impairs the phagocytosis capacity and dysregulates the key functions of MDDCs, which could mechanistically explain the observed immunotoxicity of this mycotoxin in vivo, and further emphasis the essentiality of reducing AFB1 levels in agricultural commodities.

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