Abstract
Toxoplasma gondii is a widespread parasite responsible for causing clinical diseases especially in pregnant and immunosuppressed individuals. Glucocorticoid-induced TNF receptor (GITR), which is also known as TNFRS18 and belongs to the TNF receptor superfamily, is found to be expressed in various cell types of the immune system and provides an important costimulatory signal for T cells and myeloid cells. However, the precise role of this receptor in the context of T. gondii infection remains elusive. Therefore, the current study investigated the role of GITR activation in the immunoregulation mechanisms induced during the experimental infection of mice with T. gondii. Our data show that T. gondii infection slightly upregulates GITR expression in Treg cells and B cells, but the most robust increment in expression was observed in macrophages and dendritic cells. Interestingly, mice infected and treated with an agonistic antibody anti-GITR (DTA-1) presented a robust increase in pro-inflammatory cytokine production at preferential sites of parasite replication, which was associated with the decrease in latent brain parasitism of mice under treatment with DTA-1. Several in vivo and in vitro analysis were performed to identify the cellular mechanisms involved in GITR activation upon infection, however no clear alterations were detected in the phenotype/function of macrophages, Tregs and B cells under treatment with DTA-1. Therefore, GITR appears as a potential target for intervention during infection by the parasite Toxoplasma gondii, even though further studies are still necessary to better characterize the immune response triggered by GITR activation during T. gondii infection.
Highlights
Toxoplasma gondii is an ubiquitous protozoan parasite that is estimated to infect one-third of the world’s human population
Considering that Glucocorticoid-induced TNF receptor (GITR) is widely expressed in different cells of the immune system and that its activation triggers the production of proinflammatory cytokines [13, 14], we evaluated the possible role of ligation-driven GITR activation in the regulation of the immune responses induced by T. gondii infection
These results suggest that GITR signaling may affect multiple cell lines during immune responses mounted against T. gondii
Summary
Toxoplasma gondii is an ubiquitous protozoan parasite that is estimated to infect one-third of the world’s human population. It can infect many species of warm-blooded animals and is a significant zoonotic and veterinary pathogen [1]. Acquired T. gondii infection in a pregnant woman can be transmitted to the fetus and may cause mental retardation, blindness, epilepsy and death. T. gondii can cause severe encephalitis via acute infection or reactivation. GITR Boosts Cellular Immunity against T. gondii design, data collection and analysis, decision to publish, or preparation of the manuscript
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