Alterations in Gut Motility and Peristaltic Reflexes During Cryptosporidium parvum Infection: Involvement of Interstitial Cells of Cajal

Abstract

Cryptosporidium parvum is an apicomplexan parasite causing cryptosporidiosis, characterized by watery diarrhea and altered intestinal motility. Interstitial cells of Cajal (ICC) serve as pacemaker cells orchestrating gut motility through generation of slow waves, yet their involvement in infectious diarrhea remains poorly understood. This study investigates the effects of C. parvum infection on ICC function, slow wave generation, and peristaltic reflexes. Neonatal mice were infected with C. parvum oocysts, and intestinal motility was assessed using spatiotemporal mapping, intracellular recordings, and immunohistochemistry. Results demonstrate that C. parvum infection caused significant disruption of ICC networks, with 45% reduction in c-Kit-positive ICC density in infected ileum (P < 0.001). Intracellular recordings revealed decreased slow wave amplitude (from 28.4 ± 2.1 to 16.8 ± 1.8 mV, P < 0.01) and frequency (from 18.2 ± 1.4 to 11.6 ± 1.2 cycles/min, P < 0.01). Spatiotemporal mapping showed impaired peristaltic wave propagation with 62% reduction in contraction amplitude and 48% decrease in propagation velocity. Mechanistically, C. parvum induced ICC apoptosis through caspase-3 activation and downregulated stem cell factor (SCF)/c-Kit signaling essential for ICC survival. Connexin-43 expression in ICC networks decreased by 58%, disrupting electrical coupling. Exogenous SCF administration partially restored ICC density and slow wave parameters. These findings establish ICC dysfunction as a key mechanism underlying motility disturbances in cryptosporidiosis and identify the SCF/c-Kit pathway as a potential therapeutic target.