Toxoplasma gondii activates NLRP12 inflammasome pathway in the BALB/c murine model

Abstract

The host resistance against Toxoplasma gondii (T. gondii) infection is related to the initiation of the immune response. The study aimed to investigate the role of the leucine-rich repeat family, pyrin domain -containing protein 12 (NLRP12), and cytoplasmic nucleotide-binding domain in the inflammasome-mediated cell death during murine toxoplasmosis. Groups of BALB/c mice (n = 10) were inoculated intraperitoneally with live tachyzoites, excretory-secretory antigens (ESAs) of T. gondii RH strain, and RPMI. The gene expression levels of NLRP12, caspase-3, caspase-1, IL-1β, IL-18, ASC, and Bcl-2 were measured in the peritoneal cells using quantitative real-time PCR, while the determination of NLRP12 protein level was measured by Western blot. Also, the intracellular reactive oxygen species (ROS) production was investigated. Quantitative and comparative analyses showed that injection of tachyzoites significantly increased NLRP12, caspase-3, caspase-1, IL-1β, IL-18, and ASC genes mRNA expression levels (p<0.01). Contrary to the acute infection, the Bcl-2 gene was significantly expressed in the ESAs group (p<0.0001). The level of NLRP12 protein was significantly higher in the mice that received tachyzoites and ESAs in comparison to the control group (p<0.0001). These findings provide an inside into the host-T. gondii interaction and NLRP12 regulation, which is important for the modulation of the immunological response.