# Comprehensive study of resveratrol associated to sulfadiazine in lymphocytes infected with Toxoplasma gondii: involvement of purinergic signaling in immune response

## TL;DR

This study explores how resveratrol affects immune responses in lymphocytes infected with Toxoplasma gondii, suggesting it could be a potential treatment for toxoplasmosis.

## Contribution

The study identifies resveratrol's role in modulating purinergic signaling and immune responses during Toxoplasma gondii infection in lymphocytes.

## Key findings

- Resveratrol increased ATP and ADP hydrolysis in infected lymphocytes.
- Resveratrol upregulated P1 and P2 purinergic receptors in T. gondii-infected lymphocytes.
- Resveratrol showed anti-inflammatory and antioxidant effects through adenosine receptors.

## Abstract

Toxoplasma gondii is a highly successful intracellular pathogen. Its success is largely achieved by the parasite’s ability to avoid the host immune response. During T. gondii infection lymphocytes play an active role in host defense and purinergic signaling has been shown to contribute to parasite control. Several studies have demonstrated the importance of ATP (adenosine triphosphate) signaling via purinergic receptor, as a component of the inflammatory response against T. gondii. Here, we hypothesized whether RSV, a natural polyphenol, could be involved in T. gondii control triggered by purinergic signaling, during acute infection in lymphocytes. Thus, the outcomes of this study were lymphocyte viability, modulation of ectonucleotidase activity, purinergic receptor expression and inflammatory mediators. T. gondii infection diminished lymphocytes viability 24h after RH-tachyzoites exposition. RSV treatment promote an increment of ATP, ADP hydrolysis by NTPDase (CD39) and adenosine deamination by ADA enzyme in infected lymphocytes. In addition, RSV upregulated P1 and P2 receptors in T. gondii-infected lymphocytes. There is an involvement of P2X7 receptor and proinflammatory cytokines in activated lymphocytes leading to ROS generation and nitrite production. However, the excessive damage is controlled by anti-inflammatory and antioxidant effects of RSV thought adenosine receptors and anti-inflammatory cytokine production. Together, our results suggest RSV isolate or combinate to sulfamethoxazole trimethoprim (choice drug for toxoplasmosis) could upregulate purinergic signaling during T. gondii infection suggesting a therapeutical candidate target in toxoplasmosis.

The online version contains supplementary material available at 10.1007/s11686-026-01252-x.