CCR5 Controls Immune and Metabolic Functions during Toxoplasma gondii Infection

Autor(es)

Bonfa, Giuliano ^[1] ; Benevides, Luciana ^[1] ; Souza, Maria do Carmo ^[1] ; Fonseca, Denise Morais ^[1] ; Patriarca Mineo, Tiago Wilson ^[2] ; Rossi, Marcos Antonio ^[3] ; Silva, Neide Maria ^[2] ; Silva, Joao Santana ^[1] ; de Barros Cardoso, Cristina Ribeiro ^[4]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Bioquim & Imunol, BR-14049 Ribeirao Preto, SP - Brazil

^[2] Univ Fed Uberlandia, Inst Ciencias Biomed, BR-38400 Uberlandia, MG - Brazil

^[3] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Patol, BR-14049 Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, BR-14049 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 9, n. 8 AUG 13 2014.
• Citações Web of Science: 8

Resumo

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-gamma, TNF, IL-6, iNOS, Foxp3, T-bet, GATA-3 and PPAR alpha. 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. PPAR alpha 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. (AU)

• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 12/14524-9 - Modulação da diferenciação de linfócitos T em infecções por protozoários, fungos e bactérias
• Beneficiário: João Santana da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Temático