Coutinho-Silva Robson, Stahl Lynn, Raymond Marie-Noëlle, Jungas Thomas, Verbeke Philippe, Burnstock Geoffrey, Darville Toni, Ojcius David M
Université Paris 7, Institut Jacques Monod, CNRS UMR 7592, 2 place Jussieu, 75251 Paris cedex 5, France.
Immunity. 2003 Sep;19(3):403-12. doi: 10.1016/s1074-7613(03)00235-8.
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.
沙眼衣原体通过抑制衣原体空泡与溶酶体之间的融合而在宿主细胞内存活。我们在此表明，用ATP处理感染的巨噬细胞会通过嘌呤能受体P2X(7)R的连接导致衣原体死亡。衣原体的杀伤需要磷脂酶D（PLD）的激活，因为PLD抑制会导致ATP处理的巨噬细胞中的衣原体得到挽救。然而，在ATP处理的P2X(7)R缺陷型巨噬细胞中没有PLD激活，也没有衣原体杀伤。P2X(7)R连接通过促进衣原体空泡与溶酶体之间的融合发挥其作用。P2X(7)R刺激也导致巨噬细胞死亡，但与溶酶体的融合先于巨噬细胞死亡，并且PLD抑制并不能阻止巨噬细胞死亡。这些结果表明，P2X(7)R连接导致PLD激活，这直接负责抑制感染。
