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.

 

Miller CM¹, Zakrzewski AM², Robinson DP³, Fuller SJ⁴, Walker RA⁵, Ikin RJ², Bao SJ⁶, Grigg ME³, Wiley JS⁷, Smith NC⁵.

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.

PMID:

26053862

[PubMed - in process]