Repeat Ascaris challenge reduces worm intensity through gastric cellular reprograming

Wu, Y.; Suarez-Reyes, C.; Kneubehl, A.; Weatherhead, J.

doi:10.1101/2024.08.29.610358

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bioRxiv · 10.1101/2024.08.29.610358

Repeat Ascaris challenge reduces worm intensity through gastric cellular reprograming

Wu, Y.·Suarez-Reyes, C.·Kneubehl, A.·Weatherhead, J.

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Abstract

Ascariasis (roundworm) is the most prevalent parasitic nematode infection worldwide, impacting approximately 500 million people predominantly in low- and middle-income countries (LMICs). While people of all ages are infected with Ascaris, infection intensity (defined by worm burden) paradoxically peaks in pre-school and school aged children but then declines with age. The cause of age-dependent Ascaris worm intensity is not well understood but may be dependent on cellular changes in mucosal barrier sites. We have previously found that the gastric mucosa is a critical barrier site for Ascaris infection. Following oral ingestion of Ascaris eggs, larvae use AMCase secreted by gastric chief cells and acid secreted by gastric parietal cells to hatch. Once hatched, larvae translocate across the gastric mucosa to initiate the larval migratory cycle. However, inducing mucosal injury with administration of Tamoxifen induces mucosa cellular changes that impairs Ascaris hatching and reduces larval translocation across the gastric mucosa. In this study we established a repeated Ascaris suum challenge mouse model and evaluated if repeated Ascaris challenge also lead to cellular changes in the gastric mucosal barrier. We found that repeated Ascaris challenge caused cellular changes in the gastric mucosa which reduced worm intensity in the liver independent of the adaptive immune response. Thus, in endemic regions, where individuals experience recurrent infection throughout their lives, gastric cellular changes may be a key mechanism leading to the observed age-dependent Ascaris worm intensity changes from childhood to adulthood.

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Wu, Y., Suarez-Reyes, C., Kneubehl, A., Weatherhead, J.. 2024-08-29. Repeat Ascaris challenge reduces worm intensity through gastric cellular reprograming. https://doi.org/10.1101/2024.08.29.610358

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