Decrease in immune function and the role of mitogen-activated protein kinase (MAPK) overactivation in apoptosis during T lymphocytes activation induced by zearalenone, deoxynivalenol, and their combinations

Abstract

Currently there are few reports on the combined immunotoxicity of zearaleone (ZEA) and deoxynivalenol (DON). Since the two coexist naturally, it is necessary to understand the immunotoxicity caused by the two mycotoxins alone and in combination. To examine T lymphocytes activation and immune effect during activation, we used mouse primary spleen T lymphocytes as the experimental material and concanavalin (Con A) as the stimulator. The effects of ZEA, DON, and their combined exposure on T lymphocytes immune related function and the relationship between the activation of the mitogen-activated protein kinase (MAPK) signaling pathway and mycotoxin induced T lymphocytes apoptosis were studied in vitro. Specifically, T lymphocytes were isolated from primary mouse splenic lymphocytes, activated by Con A and then exposed to different concentrations of ZEA, DON, and their combinations. Our results showed that ZEA and DON alone and their combinations (20:1) can decrease the cell viability of T lymphocytes activated by Con A. The inhibitory effect of the combined groups was greater than that of the single mycotoxins, showing a synergistic effect. In addition, single or combined mycotoxins can lead to intracellular and surface ultrastructure damage of T lymphocytes, inhibit the expression of CD25 and CD278 and inhibit the synthesis of effect molecules poreforming protein (PFP), granzyme A (GZMA), and tumor necrosis factor-α (TNF-α). Meanwhile, the single mycotoxin or combined mycotoxins can promote the apoptosis of T lymphocytes which was accompanied by the overactivation of MAPK. After using the inhibitors of extracellular regulated protein kinases (ERK) and c-Jun N-terminal kinase (JNK) in the MAPK pathway, we found that the apoptosis of the cells induced by the ZEA was significantly decreased, and the apoptosis of the cells induced by DON had no significant changes. This suggests that the activation of MAPK induced by ZEA can promote the apoptosis of T lymphocytes, but the activation of MAPK induced by DON is not directly related to T cell apoptosis.