Aflatoxin B1 interferes with the antigen-presenting capacity of porcine dendritic cells

Abstract

Aflatoxins (AFs) are harmful to animal and human health upon consumption of AF-contaminated feed or food. Among many forms of AFs, aflatoxin B1 (AFB1) is the most toxic and carcinogenic. In addition, AFB1 impairs cell-mediated immunity, although the exact mechanism of this immunotoxicity is currently unknown. By far the most pivotal cells in the induction of immune responses are dendritic cells (DCs). These highly specialised cells dictate T-cell polarisation depending on the nature of the encountered antigens and environmental cues. To elucidate the effect of AFB1 on the function of DCs, we used porcine monocyte-derived DCs (MoDCs) as a model system. A low dose of AFB1 transiently reduced the phagocytic capacity of MoDCs. Furthermore, as compared to untreated MoDCs, AFB1 significantly downregulated the cell surface expression of the co-stimulatory molecule CD40 at 12h post treatment, while at 24h the membrane expression levels of CD40 and the activation marker CD25 were significantly upregulated. Interestingly, the T-cell proliferation-inducing capacity of DCs was diminished upon AFB1 treatment. In contrast, the cytokine secretion pattern of AFB1-treated MoDCs was similar to mock-treated MoDCs. The results in this study indicate that a low level of AFB1 dysregulates the antigen-presenting capacity of DCs, which could explain the observed immunotoxicity of this mycotoxin, and further stress the need to reduce AFB1 levels in agricultural commodities.