Receptor for advanced glycation end products regulates the pulmonary and intestinal host responses to the infection with the parasitic nematode Nippostrongylus brasiliensis.

Parasitic nematode infection elicits goblet and tuft cell hyperplasia in host intestinal mucosa, resulting in the expulsion of intestinal nematodes. The receptor for advanced glycation end products (RAGE, alias Ager) is associated with pro-inflammatory responses following invasion by intestinal nematodes. We found here that the survival rate of RAGE-deficient Ager-null mice infected with Nippostrongylus brasiliensis (N. brasiliensis) larvae was higher than that of wild-type (WT) mice. In the lungs of infected mice, the destruction of the pulmonary alveoli was less pronounced in Ager-null mice than in WT mice, although the worm burden was comparable. In the small intestine of the infected mice, the number of adult worms was lower in Ager-null mice than in WT mice, whereas the number of goblet and tuft cells was higher. Moreover, the expression levels of COX2/Ptgs2 and prostaglandin D2 (PGD2) synthase transcripts were lower in infected Ager-null mice than in infected WT mice. Furthermore, intraperitoneal injection of PGD2 interfered with goblet and tuft cell hyperplasia in the small intestines of infected Ager-null mice. Taken together, these findings indicate that RAGE induces severe pulmonary damage, alleviates goblet and tuft cell hyperplasia in the small intestinal mucosa through the production of PGD2, and facilitates worm parasitism.