Endothelial cells protect Schistosoma mansoni from hydrogen peroxide-induced death

Schistosoma mansoni, the causative agent of intestinal schistosomiasis, thrives in the human host, particularly within the vascular system. Understanding the role of endothelial cells during infection is crucial. Currently, schistosomiasis treatment depends solely on praziquantel (PZQ), but emerging evidence suggests decreasing efficacy. This highlights the need for new therapeutic strategies, including agents that modulate the host antioxidant response, such as dapsone.

Adult S. mansoni worms were harvested from infected mice via portal perfusion. Human umbilical vein endothelial cells (HUVECs) were cultured and exposed to worm pairs and PZQ for 1, 3, or 6 hours. Post-exposure, RNA was extracted and analyzed by qPCR to assess the expression of antioxidant genes (NRF2, SOD1, GPx, GSR, CAT). Additionally, worm viability under oxidative stress was evaluated by incubating worms with hydrogen peroxide (H₂O₂), in the presence or absence of HUVECs, catalase, or dapsone hydroxylamine.

Worms did not significantly alter expression of host antioxidant genes except for catalase. H₂O₂ exposure led to worm death, but co-incubation with HUVECs improved worm viability and survival, suggesting a protective role of endothelial cells against oxidative stress. Furthermore, dapsone hydroxylamine reversed the protective effect of catalase, reducing worm viability. However, worms remained viable in co-culture with HUVECs, indicating additional, unidentified mechanisms of protection.

Endothelial cells may play a key role in protecting S. mansoni against host oxidative defenses. Dapsone hydroxylamine interferes with this protection by inhibiting catalase activity. These findings point to potential therapeutic strategies targeting the host-parasite interface and the antioxidant environment in schistosomiasis.