title: The role of the P2X7 receptor in murine cutaneous leishmaniasis: aspects of inflammation and parasite control.
abstract: Leishmania amazonensis is the etiological agent of diffuse cutaneous leishmaniasis. The immunopathology of leishmaniasis caused by L. amazonensis infection is dependent on the pathogenic role of effector CD4+T cells. Purinergic signalling has been implicated in resistance to infection by different intracellular parasites. In this study, we evaluated the role of the P2X7 receptor in modulating the immune response and susceptibility to infection by L. amazonensis. We found that P2X7-deficient mice are more susceptible to L. amazonensis infection than wild-type (WT) mice. P2X7 deletion resulted in increased lesion size and parasite load. Our histological analysis showed an increase in cell infiltration in infected footpads of P2X7-deficient mice. Analysis of the cytokine profile in footpad homogenates showed increased levels of IFN-γ and decreased TGF-β production in P2X7-deficient mice, suggesting an exaggerated pro-inflammatory response. In addition, we observed that CD4+and CD8+T cells from infected P2X7-deficient mice exhibit a higher proliferative capacity than infected WT mice. These data suggest that P2X7 receptor plays a key role in parasite control by regulating T effector cells and inflammation during L. amazonensis infection.
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, IBCCF/Federal University of Rio de Janeiro - UFRJ, Rio de Janeiro, RJ, 21941-902, Brazil.|National Institute of Science and Technology for Translational Research in Health and Environment in the Amazon Region (INPeTAm), Rio de Janeiro, Brazil.
authors.forename: Vanessa Ribeiro
authors.initials: VR
authors.lastname: Figliuolo
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, IBCCF/Federal University of Rio de Janeiro - UFRJ, Rio de Janeiro, RJ, 21941-902, Brazil.|National Institute of Science and Technology for Translational Research in Health and Environment in the Amazon Region (INPeTAm), Rio de Janeiro, Brazil.
authors.forename: Suzana Passos
authors.initials: SP
authors.lastname: Chaves
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, IBCCF/Federal University of Rio de Janeiro - UFRJ, Rio de Janeiro, RJ, 21941-902, Brazil.|National Institute of Science and Technology for Translational Research in Health and Environment in the Amazon Region (INPeTAm), Rio de Janeiro, Brazil.
authors.forename: Luiz Eduardo Baggio
authors.initials: LEB
authors.lastname: Savio
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, IBCCF/Federal University of Rio de Janeiro - UFRJ, Rio de Janeiro, RJ, 21941-902, Brazil.
authors.forename: Maria Luiza Prates
authors.initials: MLP
authors.lastname: Thorstenberg
authors.affiliation: Immunology Department, University of São Paulo - USP, São Paul, Brazil.
authors.forename: Érika
authors.initials: É
authors.lastname: Machado Salles
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, IBCCF/Federal University of Rio de Janeiro - UFRJ, Rio de Janeiro, RJ, 21941-902, Brazil.
authors.forename: Christina Maeda
authors.initials: CM
authors.lastname: Takiya
authors.affiliation: Immunology Department, University of São Paulo - USP, São Paul, Brazil.
authors.forename: Maria Regina
authors.initials: MR
authors.lastname: D'Império-Lima
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, IBCCF/Federal University of Rio de Janeiro - UFRJ, Rio de Janeiro, RJ, 21941-902, Brazil.
authors.forename: Herbert Leonel
authors.initials: HL
authors.lastname: de Matos Guedes
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, IBCCF/Federal University of Rio de Janeiro - UFRJ, Rio de Janeiro, RJ, 21941-902, Brazil.|National Institute of Science and Technology for Translational Research in Health and Environment in the Amazon Region (INPeTAm), Rio de Janeiro, Brazil.
authors.forename: Bartira
authors.initials: B
authors.lastname: Rossi-Bergmann
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, IBCCF/Federal University of Rio de Janeiro - UFRJ, Rio de Janeiro, RJ, 21941-902, Brazil. rcsilva@biof.ufrj.br.|National Institute of Science and Technology for Translational Research in Health and Environment in the Amazon Region (INPeTAm), Rio de Janeiro, Brazil. rcsilva@biof.ufrj.br.|Instituto de Biofísica Carlos Chagas Filho - UFRJ, Edifício do Centro de Ciências da Saúde, Bloco G. Av. Carlos Chagas Filho, 373. Cidade Universitária, Ilha do Fundão, Rio de Janeiro, RJ, 21941-902, Brazil. rcsilva@biof.ufrj.br.
authors.forename: Robson
authors.initials: R
authors.lastname: Coutinho-Silva
mesh_terms: D000818:Animals; D007249:Inflammation / Q000276:immunology; D016774:Leishmaniasis, Diffuse Cutaneous / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058486:Receptors, Purinergic P2X7 / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D058486:Receptors, Purinergic P2X7
keywords: ATP; L. amazonensis; Macrophages; P2X7; T cells