title: Inflammatory early events associated to the role of P2X7 receptor in acute murine toxoplasmosis.
abstract: Activation of the purinergic P2X7 receptor by extracellular ATP (eATP) potentiates proinflammatory responses during infections by intracellular pathogens. Extracellular ATP triggers an antimicrobial response in macrophages infected with Toxoplasma gondii in vitro, suggesting that purinergic signaling may stimulate host defense mechanisms against toxoplasmosis. Here, we provide in vivo evidence in support of this hypothesis, by showing that P2X7-/-mice are more susceptible than P2X7+/+mice to acute infection by the RH strain of T. gondii, and that this phenomenon is associated with a deficient proinflammatory response. Four days post-infection, peritoneal washes from infected P2X7-/-mice had no or little increase in the levels of the proinflammatory cytokines IL-12, IL-1β, IFN-γ, and TNF-α, whose levels increased markedly in samples from infected P2X7+/+mice. Infected P2X7-/-mice displayed an increase in organ weight and histological alterations in some of the 'shock organs' in toxoplasmosis - the liver, spleen and mesenteric lymph nodes. The liver of infected P2X7-/-mice had smaller granulomas, but increased parasite load/granuloma. Our results confirm that the P2X7 receptor is involved in containing T. gondii spread in vivo, by stimulating inflammation.
authors.affiliation: Laboratório de Imunofisiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil; Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: Gladys
authors.initials: G
authors.lastname: Corrêa
authors.affiliation: Laboratório de Imunofisiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: Carolina de
authors.initials: C
authors.lastname: Almeida Lindenberg
authors.affiliation: Laboratório de Imunofisiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: Aline Cristina de Abreu
authors.initials: AC
authors.lastname: Moreira-Souza
authors.affiliation: Laboratório de Imunofisiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: Luiz Eduardo Baggio
authors.initials: LE
authors.lastname: Savio
authors.affiliation: Laboratório de Imunofisiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: Christina Maeda
authors.initials: CM
authors.lastname: Takiya
authors.affiliation: Laboratório de Imunofisiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Marques-da-Silva
authors.affiliation: Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil. Electronic address: vommaro@biof.ufrj.br.
authors.forename: Rossiane Claudia
authors.initials: RC
authors.lastname: Vommaro
authors.affiliation: Laboratório de Imunofisiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil. Electronic address: rcsilva@biof.ufrj.br.
authors.forename: Robson
authors.initials: R
authors.lastname: Coutinho-Silva
mesh_terms: D000818:Animals; D001706:Biopsy; D016207:Cytokines / Q000378:metabolism; D005260:Female; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D018836:Inflammation Mediators / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D059208:Parasite Load; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology* / Q000378:metabolism* / Q000401:mortality / Q000469:parasitology; D014124:Toxoplasmosis, Animal
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D058486:Receptors, Purinergic P2X7
keywords: Inflammatory response; P2X7 receptor; Purinergic signaling; Toxoplasma gondii