Animals without IRAK-4 are more susceptible to viruses and bacteria but completely resistant to LPS challenge.
In addition to its effects on chloride secretion, which involve the same steps as the effects of cholera toxin, heat-labile enterotoxin binds additional substrates: lipopolysaccharide on the surface of E. coli cells and A-type blood antigens.
The second hit is characterized by an activation of the Toll-like receptor 4 (TLR4) and CD14, receptors on the Kupffer cell that internalize endotoxin (lipopolysaccharide or LPS).