Inflammatory early events associated to the role of P2X7 receptor in acute murine toxoplasmosis.

Autor: Corrêa G; 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., Almeida Lindenberg C; Laboratório de Imunofisiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil., Moreira-Souza AC; Laboratório de Imunofisiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil., Savio LE; Laboratório de Imunofisiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil., Takiya CM; Laboratório de Imunofisiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil., Marques-da-Silva C; Laboratório de Imunofisiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil., Vommaro RC; 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., Coutinho-Silva R; Laboratório de Imunofisiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil. Electronic address: rcsilva@biof.ufrj.br.
Jazyk: angličtina
Zdroj: Immunobiology [Immunobiology] 2017 Apr; Vol. 222 (4), pp. 676-683. Date of Electronic Publication: 2016 Dec 30.
DOI: 10.1016/j.imbio.2016.12.007
Abstrakt: 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.
(Copyright © 2016 Elsevier GmbH. All rights reserved.)
Databáze: MEDLINE
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