Title

Inhibition of chlamydial infectious activity due to P2X7 receptor-dependent phospholipase D activation

ORCiD

David M. Ojcius: 0000-0003-1461-4495

Document Type

Article

Publication Title

Immunity

ISSN

1074-7613

Volume

19

Issue

3

DOI

10.1016/S1074-7613(03)00235-8

First Page

403

Last Page

412

Publication Date

9-1-2003

Abstract

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, P2X7R. 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 P2X7R-deficient macrophages. P2X7R ligation exerts its effects by promoting fusion between Chlamydia vacuoles and lysosomes. P2X7R 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 P2X7R ligation leads to PLD activation, which is directly responsible for inhibition of infection.