Immunobiologically relevant level of aflatoxin B1 alters transcription of key functional immune genes, phagocytosis and survival of human dendritic cells

Abstract

The effects of naturally occurring levels of aflatoxin (AF) B1 on the expression of key molecules and function of dendritic cells (DCs) were investigated on human monocyte-derived DCs (MDDCs) by cell culture, RT-qPCR, and flow cytometry. An environmentally relevant level of AFB1 remarkably impaired the phagocytic capacity of MDDCs. Furthermore, AFB1 significantly affected the transcript levels of some key functional genes in MDDCs. It caused an up-regulation of key transcripts in cytochrome P450 (CYP) family, MyD88, NF-KB, TNF-α, TLR2, TLR4, COX-2, HLA-DR, CCR7, CD209, LFA3 and CD16. AFB1 down-regulated the expression of AhR, TGF-β, CD11c and CD64 within 2–12 h post-exposure. In contrast, the transcription of some other key genes, including IL-10, IL-1β, AKR7A2, GSTM1, IL-6. IL-8 and C5aR in post-AFB1 treated MDDCs was only slightly changed. The results indicate that an environmentally relevant level of AFB1 impairs the phagocytosis capacity of MDDCs and dysregulates the key functions in these pivotal immune cells. This could provide a mechanistic explanation for the observed in vivo immunotoxicity associated with this mycotoxin, and further emphasize the essential need for reduction of AFB1 levels in agricultural commodities.