The CGM1a (CEACAM3/CD66d)-mediated phagocytic pathway of Neisseria gonorrhoeae expressing opacity proteins is also the pathway to cell death

Phagocytosis of Opa(+) Neisseria gonorrhoeae (gonococcus, GC) by neutrophil s is in part dependent on the interaction of Opa proteins with CGM1a (CEACA M3/CD66d) antigens, a neutrophil-specific receptor. However, the signaling pathways leading to phagocytosis have not been characterized. Here we show that interaction of Opal bacteria with neutrophils or CGM1a-transfected DT4 0 cells induces calcium flux, which correlates with phagocytosis of bacteri a. We identified an immunoreceptor tyrosine-based activation motif (ITAM) i n CGM1a, and showed that the ability of CGM1a to transduce signals and medi ate phagocytosis was abolished by mutation of the ITAM tyrosines. We also d emonstrated that CGM1a-ITAM-mediated bacterial phagocytosis is dependent on Syk and phospholipase C activity in DT40 cells. Unexpectedly, the activati on of the CGM1a-ITAM phagocytic pathway by Opa(+) GC results in induction o f cell death.