Connection Between Toxoplasma Gondii Infection & CF Could Lead To Effective, New Therapies

Researchers have discovered an association between Cystic Fibrosis and infection with the parasite Toxoplasma gondii. The study entitled “Infection by Toxoplasma gondii, a severe parasite in neonates and AIDS patients, causes impaired anion secretion in airway epithelia” was published in the Proceedings of the National Academy of Sciences of the United States of America. This study revealed a link between a crucial chloride pump altered in patients with cystic fibrosis and the parasite Toxoplasma, which could lead into new insights into how to treat serious bacterial infections in those with the disease.

Cystic fibrosis (CF) affects various organs and is characterized by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein, an epithelial anion channel mainly responsible for trans-epithelial secretion of chloride (Cl^–) and bicarbonate ions. This secretion mechanism plays an important role in mucociliary removal of inhaled pathogens. Toxoplasma gondii (T. gondii), an opportunistic intracellular protozoan parasite and one of the most frequent in humans that can cause pulmonary disease in newborns, children, and immunocompromised individuals. However, it is not well understood how T. gondii infection affects airway epithelia.

The research team investigated the effects of T. gondii on Cl⁻ secretion of the mouse tracheal epithelia. The team found that the T. gondii parasite affected the normal function of the chloride secretion system. In patients with cystic fibrosis and pneumonia, this secretion mechanism is not functional. This defect was associated with infection by the T. gondii parasite, leading researchers to discover that a receptor called ‘P2Y2-R,’ which is responsible for switching on this secretion mechanism, is inhibited during T. gondii infection.

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This study revealed the impact of pathological changes in P2Y2-R on downstream signals, suggesting that P2Y2-R may be involved in the mechanism causing T. gondii infection in airways. These findings connect T. gondii infection and possibly other pathogen infections to Cl⁻ secretion through P2Y2-R. This new understanding may contribute to the development of novel potential therapies for pneumonia caused by pathogens such as T. gondii.

In addition to potentially benefitting CF patients, the discovery can also help treat people throughout the world affected by the T. gondii infection who do not have the disease. “This is a very important finding as this parasite is thought to infect around 10% of people in the UK and 30% of people globally,” said Professor Hide in the news release.

Professor Hide highlighted also the importance of understanding the parasite biology for the development of future therapies.