Lack of a Functioning P2X7 Receptor Leads to Increased Susceptibility to Toxoplasmic Ileitis

PLoS One. 2015 Jun 8;10(6):e0129048. doi: 10.1371/journal.pone.0129048. eCollection 2015.

Abstract

Background: Oral infection of C57BL/6J mice with the protozoan parasite Toxoplasma gondii leads to a lethal inflammatory ileitis.

Principal findings: Mice lacking the purinergic receptor P2X7R are acutely susceptible to toxoplasmic ileitis, losing significantly more weight than C57BL/6J mice and exhibiting much greater intestinal inflammatory pathology in response to infection with only 10 cysts of T. gondii. This susceptibility is not dependent on the ability of P2X7R-deficient mice to control the parasite, which they accomplish just as efficiently as C57BL/6J mice. Rather, susceptibility is associated with elevated ileal concentrations of pro-inflammatory cytokines, reactive nitrogen intermediates and altered regulation of elements of NFκB activation in P2X7R-deficient mice.

Conclusions: Our data support the thesis that P2X7R, a well-documented activator of pro-inflammatory cytokine production, also plays an important role in the regulation of intestinal inflammation.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Disease Models, Animal
  • Disease Progression
  • Disease Susceptibility*
  • Ileitis / genetics*
  • Ileitis / metabolism
  • Ileitis / parasitology*
  • Ileitis / pathology
  • Inflammation Mediators / metabolism
  • MAP Kinase Signaling System
  • Male
  • Mice
  • Mice, Knockout
  • NF-kappa B / metabolism
  • Reactive Nitrogen Species / metabolism
  • Receptors, Purinergic P2X7 / deficiency*
  • Toxoplasma*
  • Toxoplasmosis, Animal / genetics*
  • Toxoplasmosis, Animal / metabolism
  • Toxoplasmosis, Animal / parasitology*

Substances

  • Cytokines
  • Inflammation Mediators
  • NF-kappa B
  • Reactive Nitrogen Species
  • Receptors, Purinergic P2X7