Host gastric corpus microenvironment facilitates Ascaris suum larval hatching and infection in a murine model.

Ascariasis (roundworm) is the most common parasitic helminth infection globally and can lead to significant morbidity in children including chronic lung disease. Children become infected with Ascaris spp. via oral ingestion of eggs. It has long been assumed that Ascaris egg hatching and larval translocation across the gastrointestinal mucosa to initiate infection occurs in the small intestine. Here, we show that A. suum larvae hatched in the host stomach in a murine model. Larvae utilize acidic mammalian chitinase (AMCase; acid chitinase; Chia) from chief cells and acid pumped by parietal cells to emerge from eggs on the surface of gastric epithelium. Furthermore, antagonizing AMCase and gastric acid in the stomach decreases parasitic burden in the liver and lungs and attenuates lung disease. Given Ascaris eggs are chitin-coated, the gastric corpus would logically be the most likely organ for egg hatching, though this is the first study directly evincing the essential role of the host gastric corpus microenvironment. These findings point towards potential novel mechanisms for therapeutic targets to prevent ascariasis and identify a new biomedical significance of AMCase in mammals. Author summary: Ascariasis is the most common helminth infection and leads to significant global morbidity. Current therapies specifically target intraluminal adult intestinal worms and do not provide sufficient protection against the Ascaris larva. To reduce Ascaris-induced morbidity, novel interventions are needed that target Ascaris larval migration which calls for a better understanding of the Ascaris larval migration cycle. After oral ingestion of Ascaris eggs, previous studies have indicated that Ascaris larval migration initiates in the small intestine. However, our study demonstrates that Ascaris larva begin the migration cycle by hatching in the stomach by using the host's acidic mammalian chitinase and stomach acid to help degrade the chitinous egg shell. The larvae subsequently translocate across the stomach mucosa in this mouse model. Our study provides the first insight that the gastric corpus microenvironment plays a critical role in Ascaris egg hatching and initiation of infection, and will aid in the identification of novel drug targets. [ABSTRACT FROM AUTHOR]