title: CCR5 controls immune and metabolic functions during Toxoplasma gondii infection.
abstract: CCR5, an important receptor related to cell recruitment and inflammation, is expressed during experimental Toxoplasma gondii infection. However, its role in the immunopathology of toxoplasmosis is not clearly defined yet. Thus, we inoculated WT and CCR5(-/-) mice with a sub lethal dose of the parasite by oral route. CCR5(-/-) mice were extremely susceptible to infection, presenting higher parasite load and lower tissue expression of IL-12p40, IFN-γ, TNF, IL-6, iNOS, Foxp3, T-bet, GATA-3 and PPARα. Although both groups presented inflammation in the liver with prominent neutrophil infiltration, CCR5(-/-) mice had extensive tissue damage with hepatocyte vacuolization, steatosis, elevated serum triglycerides and transaminases. PPARα agonist Gemfibrozil improved the vacuolization but did not rescue CCR5(-/-) infected mice from high serum triglycerides levels and enhanced mortality. We also found intense inflammation in the ileum of CCR5(-/-) infected mice, with epithelial ulceration, augmented CD4 and decreased frequency of NK cells in the gut lamina propria. Most interestingly, these findings were accompanied by an outstanding accumulation of neutrophils in the ileum, which seemed to be involved in the gut immunopathology, once the depletion of these cells was accompanied by reduced local damage. Altogether, these data demonstrated that CCR5 is essential to the control of T. gondii infection and to maintain the metabolic, hepatic and intestinal integrity. These findings add novel information on the disease pathogenesis and may be relevant for directing future approaches to the treatment of multi-deregulated diseases.
authors.affiliation: Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Bonfá
authors.affiliation: Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Benevides
authors.affiliation: Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Maria do Carmo
authors.initials: Mdo C
authors.lastname: Souza
authors.affiliation: Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Denise Morais
authors.initials: DM
authors.lastname: Fonseca
authors.affiliation: Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil.
authors.forename: Tiago Wilson Patriarca
authors.initials: TW
authors.lastname: Mineo
authors.affiliation: Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Marcos Antônio
authors.initials: MA
authors.lastname: Rossi
authors.affiliation: Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil.
authors.forename: Neide Maria
authors.initials: NM
authors.lastname: Silva
authors.affiliation: Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: João Santana
authors.initials: JS
authors.lastname: Silva
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Cristina Ribeiro
authors.initials: CR
authors.lastname: de Barros Cardoso
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D015248:Gemfibrozil; D055786:Gene Knockout Techniques; D007082:Ileum / Q000276:immunology / Q000473:pathology; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D019713:Receptors, CCR5 / Q000235:genetics* / Q000276:immunology*; D018709:Statistics, Nonparametric; D014123:Toxoplasmosis / Q000276:immunology* / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood
chemical_list: C000592874:CCR5 protein, mouse; D016207:Cytokines; D017931:DNA Primers; D019713:Receptors, CCR5; D014280:Triglycerides; D015248:Gemfibrozil