Unraveling the molecular mechanism by which NetB triggers intestinal disease in chickens: from target cell to host response

One of the most important diseases that is challenging the poultry industry worldwide is necrotic
enteritis (NE). The causative agent of NE is Clostridium perfringens. Today, antibiotics are the most
effective control method to control NE, but alternative strategies are essential to comply with the
growing consumer demand for antibiotic reduction in the animal production industry. In order to
establish a targeted method to intervene with NE pathogenesis, a profound knowledge of the
molecular mechanisms that drive this disease is needed. NetB is essential for the development of
necrotic lesions in the intestine. However, little is known about the in vivo target and host
response to NetB during disease. As NE is clearly a toxin-mediated disease, understanding the
molecular basis by which this toxin exerts its effects will cause a large scientific impact that can
subsequently lead to rational design of control methods.
We hypothesize that NetB targets a specific cell type in the intestinal mucosa through binding with
an unknown, cell-specific receptor. Binding of NetB to this receptor leads to the activation of
various signal transduction pathways which eventually cause influx of inflammatory cells and
mucosal necrosis. To test this hypothesis, we will identify and isolate the cells targeted by NetB,
identify the receptor responsible for the cell-specific action of NetB and finally characterize the
host responses specifically linked to NetB.