Disruption of Purinergic Receptor P2X7 Signaling Increases Susceptibility to Cerebral Toxoplasmosis.

Abstract

Toxoplasmosis is a neglected disease that affects millions of individuals worldwide. Toxoplasma gondii infection is an asymptomatic disease, with lethal cases occurring mostly in HIV patients and organ transplant recipients. Nevertheless, atypical strains of T. gondii in endemic locations cause severe pathology in healthy individuals. Toxoplasmosis has no cure but it can be controlled by the proinflammatory immune response. The purinergic receptor P2X7 (P2X7) is involved in many inflammatory events and has been associated with genes that confer resistance against toxoplasmosis in humans. In vitro studies have reported parasite death after P2X7-receptor activation in various cell types. To understand the contribution of P2X7 during cerebral toxoplasmosis, wild-type and P2rx7 knockout mice were infected orally with T. gondii and their pathologic profiles were analyzed. We found that all P2rx7-/- mice died 8 weeks after infection with an increased number of cysts and fewer inflammatory infiltrates in their brains. The cytokines interleukin-1β, interleukin-12, tumor necrosis factor-α, and reactive oxygen species were absent or reduced in P2rx7-/- mice. Taken together, these data suggest that the P2X7 receptor promotes inflammatory infiltrates, proinflammatory cytokines, and reactive oxygen species production in the brain, and that P2X7 signaling mediates major events that confer resistance to cerebral toxoplasmosis.

• Authors: Aline Cristina Abreu Moreira-Souza, Thuany Prado Rangel, Sthefani Rodrigues Batista da Silva, Vanessa Ribeiro Figliuolo, Luiz Eduardo Baggio Savio, Felipe Schmitz, Christina Maeda Takiya, Angela T S Wyse, Rossiane Claudia Vommaro, Robson Coutinho-Silva
• Journal: The American journal of pathology (Am J Pathol) Vol. 189 Issue 4 Pg. 730-738 (04 2019) ISSN: 1525-2191 [Electronic] United States
• PMID: 30653952 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Cytokines
• Inflammation Mediators
• P2rx7 protein, mouse
• Receptors, Purinergic P2X7

Topics

• Animals
• Brain (metabolism, microbiology, pathology)
• Cytokines (metabolism)
• Disease Susceptibility
• Female
• Inflammation (etiology, metabolism, pathology)
• Inflammation Mediators (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Receptors, Purinergic P2X7 (physiology)
• Signal Transduction
• Toxoplasma (pathogenicity)
• Toxoplasmosis, Cerebral (etiology, metabolism, pathology)