Mycotoxins is a unwanted contaminant on grain, corn and fruits and are reported to be found in increasing amounts also in processed food. There is an increasing focus on mycotoxins worldwide regarding their deleterious effects alone or in combinations, towards humans and production animals. Mycotoxin exposure occurs via food and air. Several mycotoxins have been reported to be toxic towards immune cells and it is questioned whether they can alter immune responses. This study is conducted to investigate the effects of the mycotoxins alternariol (AOH), enniatin B (EnnB), deoxynivalenol (DON), satratoxin G (SG), and roridin A (RA) on macrophages and to compare results from the macrophage cell line RAW 264.7 with primary human macrophages. The various mycotoxins effects on macrophages were studied by proliferation assay, apoptosis measurements, cytokine secretion, Reactive oxygen measurements, microscopy, surface receptor analysis and endocytosis assay.
This study has found that the mycotoxins were toxic towards the macrophages in both systems with a rather similar potency; RA > SG >>> DON >> EnnB > AOH. In RAW 264.7 cells AOH and EnnB induced mainly necrosis, while DON, SG and RA gave a mixture of necrosis and apoptosis. The type of specific cell death in primary human macrophage remains to be explored. EnnB induced increased IL-1β secretion in LPS primed RAW 264.7 cells, however no increase was found in LPS primed human primary macrophages. The opposite seems to be the case for DON. The morphology was clearly changed after AOH and EnnB exposure to RAW 264.7 cells. AOH treated cells were morphological similar to dendritic/M1 macrophages and were found to have a M1 phenotypic expression of surface receptors analyzed on flow cytometry. The human macrophages were also dramatically altered when exposed to AOH but surface receptor expression did not reveal a distinct phenotype despite being altered compared to control. Exposure to EnnB in human macrophages did not induce clear morphologic or phenotypic changes. The trichothecenes DON, SG and RA gave no clear morphologic change to the RAW 264.7 cell line or primary macrophages.
We hypothesize that the observed morphological and phenotypic changes seen here in AOH exposed macrophages in vitro may have implications for immune responses in vivo. This suggestion, however, needs further substantiation.