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

Immunobiology. 2016 Dec 30. pii: S0171-2985(16)30461-2. doi: 10.1016/j.imbio.2016.12.007. [Epub ahead of print]

Corrêa G¹, Almeida Lindenberg C², Moreira-Souza AC², Savio LE², Takiya CM², Marques-da-Silva C², Vommaro RC³, Coutinho-Silva R⁴.

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.

KEYWORDS:

Inflammatory response; P2X7 receptor; Purinergic signaling; Toxoplasma gondii

PMID:

28069296

DOI:

10.1016/j.imbio.2016.12.007