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Modulation of P2Z/P2X(7) receptor activity in macrophages infected with Chlamydia psittaci
R Coutinho-Silva1, J L Perfettini, P M Persechini
1Unité de Biologie des Interactions Cellulaires, Centre National de la Recherche Scientifique, Unité de Recherche Associée 1960, Institut Pasteur, 75724 Paris Cedex 15, France. rcsilva@ibccf.biof.ufrj.br
Abstract:
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/P2X(7) 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/P2X(7) 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 Ca(2+) influx previously associated with ATP(o)-induced apoptosis.
Insights
Extracellular ATP (ATP(o)) inhibits chlamydial growth in macrophages. However, Chlamydia infection impairs ATP(o)-induced apoptosis, a key immune response, suggesting a survival mechanism for the pathogen.
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Background:
- Extracellular ATP (ATP(o)) plays a role in inflammatory responses and controlling mycobacterial growth.
- ATP(o) can induce apoptosis in macrophages via P2Z/P2X(7) purinergic receptors.
Purpose of the Study:
- To investigate the effect of ATP(o) on chlamydiae viability within macrophages.
- To determine if Chlamydia infection alters macrophage susceptibility to ATP(o)-induced apoptosis.
Main Methods:
- J774 macrophage apoptosis was induced by ATP(o) and inhibited by oxidized ATP.
- Intracellular chlamydiae growth was assessed after incubation with ATP(o).
- Macrophage susceptibility to ATP(o)-mediated apoptosis was evaluated in infected cells.
Main Results:
- ATP(o) selectively triggered macrophage apoptosis, inhibited by oxidized ATP.
- Incubation with ATP(o) inhibited intracellular chlamydiae growth.
- Chlamydial infection for 24 hours reduced ATP(o)-induced apoptosis by decreasing macrophage permeability and abrogating Ca(2+) influx.
Conclusions:
- ATP(o) exhibits antimicrobial activity against intracellular chlamydiae.
- Chlamydia infection confers partial protection to host cells by modulating ATP(o)-mediated apoptosis, potentially aiding pathogen survival.