# Toxoplasma gondii chronic infection decreases visceral nociception through peripheral opioid receptor signaling

## TL;DR

A common parasite, Toxoplasma gondii, reduces gut pain in mice through the body's natural opioid system, unlike other gut infections that can cause chronic pain.

## Contribution

The study reveals a novel pain-relieving effect of chronic T. gondii infection via opioid signaling, not involving T cell-derived enkephalins.

## Key findings

- Latent T. gondii infection decreases visceral nociception in mice.
- Opioid signaling is essential for the pain-relieving effect of T. gondii.
- T cell-derived enkephalins are not responsible for the hypoalgesia observed.

## Abstract

By eliciting immune activation in the digestive tract, intestinal pathogens may perturb gut homeostasis. Some gastrointestinal infections can indeed increase the risk of developing post-infectious irritable bowel syndrome (PI-IBS). Intriguingly, the prevalent foodborne parasite Toxoplasma gondii has not been linked to the development of PI-IBS and the impact of this infection on colon homeostasis remains ill-defined. We show in a mouse model that latent T. gondii decreases visceral nociceptive responses in an opioid signaling-dependent manner. Despite the accumulation of Th1 and cytotoxic T cells in the colon of latently infected mice, the selective invalidation of enkephalin gene in T cells ruled out the involvement of T cell-derived enkephalins in hypoalgesia. These findings provide clues about how this widespread infection durably shapes the gut immune landscape and modifies intestinal physiological parameters. They suggest that in contrast to other gut microbes, T. gondii infection could be negatively associated with abdominal pain.

Toxoplasma gondii is a common parasite that infects many people worldwide, often without causing noticeable symptoms. Gut infections can lead to long-term digestive issues, like post-infectious irritable bowel syndrome (PI-IBS). Although T. gondii is a gut infection agent, it has not been linked to PI-IBS so far. In this study performed in an experimental mouse model, we examined how T. gondii latent infection affects the gut. We unexpectedly discovered that chronically infected mice experience less gut pain compared to uninfected animals. This effect is linked to the body’s natural pain-relief system, involving opioid molecules. This infection also led to long-lasting changes in immune cells of the gut, including T lymphocytes. Since T cells can produce opioids, we suspected them to play a role in the reduced pain phenotype. However, mice lacking a key opioid in their T lymphocytes still showed the same pain decrease, excluding this possible mechanism. In summary, these findings suggest that, unlike other gut infections, latent T. gondii infection may have a pain-relieving rather than a pain-inducing effect. They help better understand how infections influence gut health in unexpected ways, and in the future, they might contribute to decipher new pain control mechanisms.