@phdthesis{01JP52R3BE5F5DDJDQDDFQT5JY,
  abstract     = {{Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhea, particularly in vulnerable populations such as children, travelers, and young animals, especially piglets. The enterotoxins secreted by ETEC, including heat-labile enterotoxin (LT) and heat-stable enterotoxins (STs), play a crucial role in inducing diarrhea. Beyond their role in gastrointestinal distress, increasing attention has been given to the immunomodulatory effects of LT and STs. Some studies explored how these toxins affect gut epithelial cells and immune cells such as macrophages, dendritic cells, B cells, and T cells. However, there is limited knowledge on how LT and STs impact neutrophils and monocytes, two critical components of the innate immune system. 
Neutrophils are the most abundant white blood cells and are essential for the first line of defense against bacterial infections via their rapid migration to infection sites and effector functions such as phagocytosis, degranulation, reactive oxygen species (ROS) production, neutrophil extracellular trap (NETs) generation as well as cytokine and chemokine production. Despite the crucial role of neutrophils in combatting bacterial infections, our understanding of how enterotoxins impact neutrophil function is limited. To address this knowledge gap, In the first set of experiments, we used LT and STa to investigate their impact on the effector functions of neutrophils. Our study reveals that pSTa does not exert any discernible effect on the function of neutrophils. In contrast, LT altered the migration and phagocytosis of neutrophils and induced the production of inflammatory factors via activation of cAMP/PKA and ERK1/2 signaling. Moreover, LT attenuated the release of NETs by neutrophils via the PKA signaling pathway.
Monocytes can differentiate into macrophages or dendritic cells and serve as a bridge between the innate and adaptive arms of the 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 the second set of experiments, we investigated the effects of theLT and the STa produced by ETEC on porcine monocytes. Our results show that STa did not affect the cell viability and effector functions of monocytes. For LT, we found that this enterotoxin decreased the cell viability of monocytes. While LT did not induce 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. Furthermore, LT triggered the production of cytokines IL-1β, IL-6 and TNF-α as well as chemokines CCL-3 and CXCL-8.
The findings of this thesis provide novel insights into the impact of LT and STa on neutrophil and monocyte function, shedding light on the underlying mechanisms that govern its immunoregulatory effects. This might help ETEC in subverting the immune system and establishing infection.}},
  author       = {{Ma, Jinglin}},
  keywords     = {{heat labile enterotoxin,heat stable enterotoxin a,neutrophils,monocytes,dysfunction,pig,enterotoxigenic Escherichia Coli}},
  language     = {{eng}},
  pages        = {{227}},
  publisher    = {{Ghent University. Faculty of Veterinary Medicine}},
  school       = {{Ghent University}},
  title        = {{Unraveling the effects of enterotoxins produced by enterotoxigenic Escherichia coli on porcine innate immune cells}},
  year         = {{2025}},
}