title: GITR Activation Positively Regulates Immune Responses against Toxoplasma gondii.
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.
authors.affiliation: Laboratório de Imunoparasitologia "Dr. Mário Endsfeldz Camargo", Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Av. Amazonas s/n, Bloco 4C, Sala 4C01, 38405-320, Uberlândia, Minas Gerais, Brazil.|Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Av. dos Bandeirantes 3900, 14049-900, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Frederico R C
authors.initials: FR
authors.lastname: Costa
authors.affiliation: Laboratório de Imunoparasitologia "Dr. Mário Endsfeldz Camargo", Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Av. Amazonas s/n, Bloco 4C, Sala 4C01, 38405-320, Uberlândia, Minas Gerais, Brazil.
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Mota
authors.affiliation: Laboratório de Imunoparasitologia "Dr. Mário Endsfeldz Camargo", Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Av. Amazonas s/n, Bloco 4C, Sala 4C01, 38405-320, Uberlândia, Minas Gerais, Brazil.
authors.forename: Fernanda M
authors.initials: FM
authors.lastname: Santiago
authors.affiliation: Laboratório de Imunoparasitologia "Dr. Mário Endsfeldz Camargo", Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Av. Amazonas s/n, Bloco 4C, Sala 4C01, 38405-320, Uberlândia, Minas Gerais, Brazil.
authors.forename: Murilo V
authors.initials: MV
authors.lastname: Silva
authors.affiliation: Laboratório de Imunoparasitologia "Dr. Mário Endsfeldz Camargo", Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Av. Amazonas s/n, Bloco 4C, Sala 4C01, 38405-320, Uberlândia, Minas Gerais, Brazil.|Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Av. dos Bandeirantes 3900, 14049-900, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Marcela D
authors.initials: MD
authors.lastname: Ferreira
authors.affiliation: Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Av. dos Bandeirantes 3900, 14049-900, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Fonseca
authors.affiliation: Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Av. dos Bandeirantes 3900, 14049-900, Ribeirão Preto, São Paulo, Brazil.
authors.forename: João S
authors.initials: JS
authors.lastname: Silva
authors.affiliation: Laboratório de Imunoparasitologia "Dr. Mário Endsfeldz Camargo", Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Av. Amazonas s/n, Bloco 4C, Sala 4C01, 38405-320, Uberlândia, Minas Gerais, Brazil.
authors.forename: José R
authors.initials: JR
authors.lastname: Mineo
authors.affiliation: Laboratório de Imunoparasitologia "Dr. Mário Endsfeldz Camargo", Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Av. Amazonas s/n, Bloco 4C, Sala 4C01, 38405-320, Uberlândia, Minas Gerais, Brazil.
authors.forename: Tiago W P
authors.initials: TW
authors.lastname: Mineo
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000494:pharmacology; D001402:B-Lymphocytes / Q000276:immunology* / Q000469:parasitology; D005260:Female; D053450:Glucocorticoid-Induced TNFR-Related Protein / Q000037:antagonists & inhibitors / Q000276:immunology*; D008297:Male; D051379:Mice; D022423:Myeloid Cells / Q000276:immunology* / Q000469:parasitology; D011247:Pregnancy; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000469:parasitology; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000188:drug therapy / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D053450:Glucocorticoid-Induced TNFR-Related Protein; C106544:Tnfrsf18 protein, mouse