ATP scavenging by the intracellular pathogen Porphyromonas gingivalis inhibits P2X7-mediated host-cell apoptosis

Area of Science:

• Immunology
• Microbiology
• Cell Biology

Background:

• The P2X7 receptor (P2X7R) is crucial for innate immunity, regulating cell death and inflammation, primarily studied in macrophages.
• Primary gingival epithelial cells are key players in oral innate immunity and express functional P2X7R, responding to ATP with apoptosis.

Purpose of the Study:

• To investigate the role of P2X7R in gingival epithelial cells during infection with Porphyromonas gingivalis.
• To elucidate the mechanism by which P. gingivalis evades P2X7R-mediated apoptosis.

Main Methods:

• Primary gingival epithelial cells were treated with ATP to induce apoptosis.
• Cells were infected with wild-type P. gingivalis and an ndk-deficient mutant.
• Extracellular ATP levels and host cell viability were measured.
• Recombinant P. gingivalis nucleoside diphosphate kinase (NDK) was used to assess its effect on ATP-mediated cell death.

Main Results:

• Gingival epithelial cells express functional P2X7R and undergo apoptosis upon ATP stimulation.
• P. gingivalis inhibits ATP-induced apoptosis and plasma membrane permeabilization in these cells.
• A secreted P. gingivalis enzyme, nucleoside diphosphate kinase (NDK), is essential for suppressing host cell apoptosis.
• NDK hydrolyzes extracellular ATP, thereby preventing P2X7R activation and subsequent cell death.

Conclusions:

• P. gingivalis utilizes secreted NDK to hydrolyze extracellular ATP, thereby inhibiting P2X7R-mediated apoptosis in gingival epithelial cells.
• NDK promotes bacterial survival by preventing host cell death, highlighting a novel immune evasion strategy.