Modulation of P2Z/P2X₇ receptor activity in macrophages infected with Chlamydia psittaci

Given the role that extracellular ATP (ATP_o)-mediated apoptosis may play in inflammatory responses and in controlling mycobacterial growth in macrophages, we investigated whether ATP_o has any effect on the viability of chlamydiae in macrophages and, conversely, whether the infection has any effect on susceptibility to ATP_o-induced killing via P2Z/P2X₇ purinergic receptors. Apoptosis of J774 macrophages could be selectively triggered by ATP_o, because other purine/pyrimidine nucleotides were ineffective, and it was inhibited by oxidized ATP, which irreversibly inhibits P2Z/P2X₇ purinergic receptors. Incubation with ATP_o but not other extracellular nucleotides inhibits the growth of intracellular chlamydiae, consistent with previous observations on ATP_o effects on growth of intracellular mycobacteria. However, chlamydial infection for 1 day also inhibits ATP_o-mediated apoptosis, which may be a mechanism to partially protect infected cells against the immune response. Infection by Chlamydia appears to protect cells by decreasing the ability of ATP_o to permeabilize macrophages to small molecules and by abrogating a sustained Ca²⁺ influx previously associated with ATP_o-induced apoptosis.