Inhibition of chlamydial infectious activity due to P2X7R-dependent phospholipase D activation.
Chlamydia trachomatis survives within host cells by inhibiting fusion between Chlamydia vacuoles and lysosomes. We show here that treatment of infected macrophages with ATP leads to killing of chlamydiae through ligation of the purinergic receptor, P2X(7)R. Chlamydial killing required phospholipase D (PLD) activation, as PLD inhibition led to rescue of chlamydiae in ATP-treated macrophages. However, there was no PLD activation nor chlamydial killing in ATP-treated P2X(7)R-deficient macrophages. P2X(7)R ligation exerts its effects by promoting fusion between Chlamydia vacuoles and lysosomes. P2X(7)R stimulation also resulted in macrophage death, but fusion with lysosomes preceded macrophage death and PLD inhibition did not prevent macrophage death. These results suggest that P2X(7)R ligation leads to PLD activation, which is directly responsible for inhibition of infection.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002690:Chlamydia Infections / Q000276:immunology / Q000378:metabolism*; D002692:Chlamydia trachomatis / Q000276:immunology; D008247:Lysosomes / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D010739:Phospholipase D / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7
C546469:P2rx7 protein, mouse; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate; D010739:Phospholipase D