# Endothelial cells protect Schistosoma mansoni from hydrogen peroxide-induced death

## TL;DR

Endothelial cells help protect the Schistosoma mansoni parasite from hydrogen peroxide, suggesting new treatment strategies for schistosomiasis.

## Contribution

The study reveals that endothelial cells protect Schistosoma mansoni from oxidative stress, and dapsone hydroxylamine can interfere with this protection.

## Key findings

- Endothelial cells protect S. mansoni worms from hydrogen peroxide-induced death.
- Dapsone hydroxylamine inhibits catalase activity and reduces worm viability.
- Worms remain viable with endothelial cells, suggesting other protective mechanisms exist.

## Abstract

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.

Schistosoma mansoni, the causative agent of the intestinal form of the disease, is well adapted to its human host. Unlike other intestinal helminths, the adult S. mansoni worm has a peculiar habitat: the vascular lumen. Despite this known fact, there is still limited information about the interaction between the adult worm and endothelial cells. Current treatment relies exclusively on praziquantel (PZQ), which has shown signs of decreasing efficacy. This underscores the urgent need for alternative therapies or drug combinations, including those that target the host’s antioxidant response - such as dapsone. We evaluated the interaction between adult worms and HUVECs, and their ability to protect the parasites from oxidative stress induced by hydrogen peroxide (H₂O₂). It was observed that the worms did not significantly alter the expression of antioxidant genes by HUVECs, except for catalase. H₂O₂ was lethal to the worms, but this effect was reversed in the presence of the endothelial cells, indicating a protective effect. We also tested dapsone hydroxylamine, which inhibited catalase activity and reduced worm viability. However, when the worms were cultured with endothelial cells, they remained viable, suggesting other protective mechanisms. These findings contribute to new therapeutic approaches against schistosomiasis.