Dysregulation of the inflammatory response to the parasite, Toxoplasma gondii, in P2X7 receptor-deficient mice

The P2X(7) receptor (P2X(7)R) is a two transmembrane receptor that is highly expressed on the surface of immune cells. Loss of function polymorphisms in this receptor have been linked to increased susceptibility to intracellular pathogens. P2X7R gene knockout (P2X(7)R(-/-); on a C57Bl/6J background), C57Bl/6J and BALB/c mice were infected with the avirulent ME49 strain of the intracellular parasite, Toxoplasma gondii. and susceptibility determined by monitoring weight loss. P2X7R(-/-) mice lost significantly more weight than C57Bl/6J mice from day 8 p.i. C57Bl/6J, in turn, lost significantly more weight than BALB/c mice. Thus, by day 10 p.i., P2X(7)R(-/-) mice had lost 5.7 +/- 0.7% of their weight versus 2.4 +/- 0.6% for C57Bl/6J mice, whereas BALB/c mice had gained 1.9 +/- 0.5%; by day 12 p.i., P2X(7)R(-/-) mice had lost 15.1 +/- 0.6%, C57Bl/6J had lost 10.1 +/- 0.8% and BALB/c had lost 4.8 +/- 0.8% of their weight. Neither parasite burden nor liver pathology was greater in the P2X(7)R(-/-) mice than in C57Bl/6J mice but BALB/c mice had significantly smaller numbers of parasites and less pathology in their livers than these strains. Absence of the P2X7 receptor did not affect IFN-gamma, IL-12, IL-1 beta, monocyte chemoattractant protein-1 (MCP-1) or TNF production. However, both P2X(7)R(-/-) and C57Bl/6J mice produced more IL-1 beta and INF than BALB/c mice. There was one important point of differentiation between the P2X(7)R(-/-) and C57Bl/6J mice, namely the significantly enhanced and prolonged production of nitric oxide, accompanied by delayed production of IL-10 in the P2X(7)R-deficient mice. (C) 2010 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.