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

Miller, Catherine M., Zakrzewski, Alana M., Ikin, Rowan J., Boulter, Nicola R., Katrib, Marilyn, Lees, Michael P., Fuller, Stephen J., Wiley, James S., and Smith, Nicholas C. (2011) Dysregulation of the inflammatory response to the parasite, Toxoplasma gondii, in P2X₇ receptor-deficient mice. International Journal for Parasitology, 41 (3-4). pp. 301-308.

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Abstract

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.

Item ID: 26356
Item Type: Article (Research - C1)
ISSN: 1879-0135
Keywords: Toxoplasma gondii; Apicomplexa; P2X₇ receptor; nitric oxide; IL-10; immunopathology
Funders: Australian Research Council Discovery Project Grant (DP666515)
Date Deposited: 29 Apr 2013 02:58
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110803 Medical Parasitology @ 70%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110707 Innate Immunity @ 30%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 40%
97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 40%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 20%
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