Wu Yifan, Suarez-Reyes Charlie, Tang Nina L, Kneubehl Alexander R, Weatherhead Jill E
Department of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of America.
William T. Shearer Center for Human Immunobiology, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, United States of America.
PLoS Negl Trop Dis. 2025 May 30;19(5):e0013141. doi: 10.1371/journal.pntd.0013141. eCollection 2025 May.
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 as ingested Ascaris larvae use acidic mammalian chitinase (AMCase) secreted by gastric chief cells and acid secreted by gastric parietal cells to hatch. After hatching, larvae translocate across the gastric mucosa to initiate the larval migratory cycle. However, mucosal injury induced by administration of Tamoxifen results in cellular changes that impair Ascaris hatching and reduce larval translocation across the gastric mucosa. Since individuals in endemic settings often experience recurrent infection throughout their lives, we set out to determine how repeated Ascaris exposures affect the gastric mucosa and the intensity of resultant infections. In this study, we established a repeated Ascaris suum challenge mouse model and found that repeated Ascaris challenge caused cellular changes in the gastric mucosa which reduced worm intensity in the liver. Importantly, these decreases in infection intensity following repeated infections occurred independent of the adaptive immune response. These findings indicate that gastric cellular changes may be a key mechanism leading to the observed age-dependent Ascaris worm intensity changes from childhood to adulthood.
蛔虫病是全球最普遍的寄生线虫感染，主要影响低收入和中等收入国家的约5亿人。虽然各年龄段的人都可能感染蛔虫，但感染强度（以虫负荷定义）在学龄前和学龄儿童中反常地达到峰值，随后随年龄下降。蛔虫感染强度随年龄变化的原因尚不完全清楚，但可能取决于黏膜屏障部位的细胞变化。我们之前发现胃黏膜是蛔虫感染的关键屏障部位，因为摄入的蛔虫幼虫利用胃主细胞分泌的酸性哺乳动物几丁质酶（AMCase）和胃壁细胞分泌的酸来孵化。孵化后，幼虫穿过胃黏膜以启动幼虫迁移周期。然而，给予他莫昔芬诱导的黏膜损伤会导致细胞变化，损害蛔虫孵化并减少幼虫穿过胃黏膜的迁移。由于流行地区的个体一生中经常反复感染，我们着手确定反复接触蛔虫如何影响胃黏膜以及由此产生的感染强度。在本研究中，我们建立了一个反复感染猪蛔虫的小鼠模型，发现反复感染猪蛔虫会导致胃黏膜细胞变化，从而降低肝脏中的虫负荷。重要的是，反复感染后感染强度的降低与适应性免疫反应无关。这些发现表明，胃细胞变化可能是导致从儿童到成人观察到的蛔虫感染强度随年龄变化的关键机制。
