inhibits spontaneous apoptosis and extends human neutrophil lifespan.

is a Gram-negative bacterium that is closely related to the highly virulent facultative intracellular pathogen, Data published by us and others demonstrate that virulence correlates directly with its ability to impair constitutive apoptosis and extend human neutrophil lifespan. In contrast, is attenuated in humans, and the mechanisms that account for this are incompletely defined. Our published data demonstrate that binds natural IgG that is present in normal human serum, which in turn, elicits NADPH oxidase activation that does not occur in response to As it is established that phagocytosis and oxidant production markedly accelerate neutrophil death, we predicted that may influence the neutrophil lifespan in an opsonin-dependent manner. To test this hypothesis, we quantified bacterial uptake, phosphatidylserine (PS) externalization, and changes in nuclear morphology, as well as the kinetics of procaspase-3, -8, and -9 processing and activation. To our surprise, we discovered that not only failed to accelerate neutrophil death but also diminished and delayed apoptosis in a dose-dependent, but opsonin-independent, manner. In keeping with this, studies of conditioned media (CM) showed that neutrophil longevity could be uncoupled from phagocytosis and that stimulated neutrophil secretion of CXCL8. Taken together, the results of this study reveal shared and unique aspects of the mechanisms used by species to manipulate neutrophil lifespan and as such, advance understanding of cell death regulation during infection.