PMID- 21044631 OWN - NLM STAT- MEDLINE DCOM- 20110617 LR - 20131121 IS - 1879-0135 (Electronic) IS - 0020-7519 (Linking) VI - 41 IP - 3-4 DP - 2011 Mar TI - Dysregulation of the inflammatory response to the parasite, Toxoplasma gondii, in P2X7 receptor-deficient mice. PG - 301-8 LID - 10.1016/j.ijpara.2010.10.001 [doi] AB - 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. P2X(7)R 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. P2X(7)R(-/-) mice lost significantly more weight than C57Bl/6J mice from day 8p.i. C57Bl/6J, in turn, lost significantly more weight than BALB/c mice. Thus, by day 10p.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 12p.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 P2X(7) receptor did not affect IFN-gamma, IL-12, IL-1beta, monocyte chemoattractant protein-1 (MCP-1) or TNF production. However, both P2X(7)R(-/-) and C57Bl/6J mice produced more IL-1beta and TNF 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. CI - Copyright (c) 2010 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved. FAU - Miller, Catherine M AU - Miller CM AD - Institute for Biotechnology of Infectious Diseases, University of Technology, Sydney, Broadway, NSW 2007, Australia. FAU - Zakrzewski, Alana M AU - Zakrzewski AM FAU - Ikin, Rowan J AU - Ikin RJ FAU - Boulter, Nicola R AU - Boulter NR FAU - Katrib, Marilyn AU - Katrib M FAU - Lees, Michael P AU - Lees MP FAU - Fuller, Stephen J AU - Fuller SJ FAU - Wiley, James S AU - Wiley JS FAU - Smith, Nicholas C AU - Smith NC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20101031 PL - England TA - Int J Parasitol JT - International journal for parasitology JID - 0314024 RN - 0 (Receptors, Purinergic P2X7) RN - 130068-27-8 (Interleukin-10) RN - 31C4KY9ESH (Nitric Oxide) SB - IM MH - Animals MH - Disease Susceptibility MH - Inflammation/*immunology/*parasitology/physiopathology MH - Interleukin-10/biosynthesis MH - Liver/parasitology/pathology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Nitric Oxide/biosynthesis MH - Receptors, Purinergic P2X7/*deficiency/genetics MH - Species Specificity MH - Toxoplasma/immunology/*pathogenicity MH - Toxoplasmosis, Animal/genetics/*immunology/parasitology/*physiopathology MH - Weight Loss EDAT- 2010/11/04 06:00 MHDA- 2011/06/18 06:00 CRDT- 2010/11/04 06:00 PHST- 2010/09/26 00:00 [received] PHST- 2010/10/04 00:00 [accepted] PHST- 2010/11/04 06:00 [entrez] PHST- 2010/11/04 06:00 [pubmed] PHST- 2011/06/18 06:00 [medline] AID - S0020-7519(10)00324-3 [pii] AID - 10.1016/j.ijpara.2010.10.001 [doi] PST - ppublish SO - Int J Parasitol. 2011 Mar;41(3-4):301-8. doi: 10.1016/j.ijpara.2010.10.001. Epub 2010 Oct 31.