Dysregulation of the inflammatory response to the parasite, Toxoplasma gondii, in P2X₇ receptor-deficient mice
Journal Publication ResearchOnline@JCUAbstract
The P2X₇ receptor (P2X₇R) 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 (P2X₇R^−/−; 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., P2X₇R^−/− 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., P2X₇R^−/− 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 P2X₇R^−/− 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-γ, IL-12, IL-1β, monocyte chemoattractant protein-1 (MCP-1) or TNF production. However, both P2X₇R^−/− and C57Bl/6J mice produced more IL-1β and TNF than BALB/c mice. There was one important point of differentiation between the P2X₇R^−/− and C57Bl/6J mice, namely the significantly enhanced and prolonged production of nitric oxide, accompanied by delayed production of IL-10 in the P2X₇R-deficient mice.
Journal
International Journal for Parasitology
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Volume
41
ISBN/ISSN
1879-0135
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Issue
3-4
Pages Count
7
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Publisher
Elsevier
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DOI
10.1016/j.ijpara.2010.10.001