Immune modulatory effects of the foodborne contaminant citrinin in mice

The mycotoxin citrinin can cause mycotoxic nephropathy, cytotoxicity and genotoxicity. To investigate the immune modulatory effects, CTN was orally administered to female BALB/c mice at the dose of 1, 5, or 10 mg/kg body weight for 14 days, and several immunotoxicity tests were performed. The populations of F4/80+ cells and CD19+ cells were significantly decreased in spleen and MLN. In MLN, CD4+, CD8+, and CD4+CD25+Foxp3+ cell populations were increased. CD8+ cells were increased but CD19+ cells were decreased in intra-epithelial, lamina propria and Peyer's patches lymphocytes. In a cell proliferation assay, along with the increased proliferative capacities of ConA-induced splenocytes and MLN cells, IFN-γ production was increased. The expression of TLR 2 was increased in spleen, but TLR 3 expression in MLN was decreased. The level of serum IgM was reduced. Furthermore, apoptosis was induced in spleen, MLN and Peyer's patches and promoted by the change in the ratio of Bax/Bcl-2 activities. Autophagy gene Atg5 and Beclin-1 were up-regulated in spleen. The expressions of IL-1β, IL-10, and TNF-α were inhibited in murine macrophage cells pre-exposed with TLR ligands. These results indicate that CTN has multiple immune modulatory effects in mice that may alter normal functions of immune system.