Enterotoxigenic Escherichia coli heat labile enterotoxin induces cell death and disrupts effector functions of porcine monocytes

Enterotoxigenic Escherichia coli (ETEC) is a common cause of diarrhea in human and animals, including pigs. Enterotoxins are important virulence factors for ETEC. Although a lot is known on the mechanism of enterotoxin-induced diarrhea, less is known about their effects on innate immune cells like monocytes. Monocytes can differentiate into macrophages and dendritic cells and play a pivotal role as a bridge between the innate and adaptive immune system. Understanding the interaction between ETEC enterotoxins and monocytes can help in the development of more effective preventive and therapeutic strategies to combat this disease. In this study, we aimed to investigate the effects of the heat labile enterotoxin (LT) and the heat stable enterotoxin a (STa) produced by ETEC on porcine monocytes. Our results show that STa did not affect the cell viability and effector functions of monocytes. LT, on the other hand, decreased the cell viability of monocytes. While LT did not alter the production of reactive oxygen species (ROS) production by monocytes, it significantly reduced ROS production induced by phorbol 12-myristate 13-acetate (PMA). In addition, LT decreased the phagocytosis of E. coli by monocytes and enhanced the survival of intracellular ETEC. Furthermore, LT triggered the production of cytokines IL-1β, IL-6 and TNF-α as well as chemokines CCL-3 and CXCL-8. Together, our results show that in contrast to STa, LT can cause cell death in monocytes and disrupt their immune effector functions, potentially acting as an immune evasion strategy to establish infection.