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• W2618906059 abstract "Abstract Francisella novicida is a Gram-negative bacterium that is closely related to the highly virulent facultative intracellular pathogen, Francisella tularensis. Data published by us and others demonstrate that F. tularensis virulence correlates directly with its ability to impair constitutive apoptosis and extend human neutrophil lifespan. In contrast, F. novicida is attenuated in humans, and the mechanisms that account for this are incompletely defined. Our published data demonstrate that F. novicida binds natural IgG that is present in normal human serum, which in turn, elicits NADPH oxidase activation that does not occur in response to F. tularensis. As it is established that phagocytosis and oxidant production markedly accelerate neutrophil death, we predicted that F. novicida 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 F. novicida 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 F. novicida stimulated neutrophil secretion of CXCL8. Taken together, the results of this study reveal shared and unique aspects of the mechanisms used by Francisella species to manipulate neutrophil lifespan and as such, advance understanding of cell death regulation during infection." @default.
• W2618906059 created "2017-06-05" @default.
• W2618906059 creator A5020947009 @default.
• W2618906059 creator A5052550075 @default.
• W2618906059 creator A5074717391 @default.
• W2618906059 date "2017-05-26" @default.
• W2618906059 modified "2023-10-17" @default.
• W2618906059 title "<i>Francisella novicida</i> inhibits spontaneous apoptosis and extends human neutrophil lifespan" @default.
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• W2618906059 doi "https://doi.org/10.1189/jlb.4ma0117-014r" @default.
• W2618906059 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5557636" @default.
• W2618906059 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28550119" @default.
• W2618906059 hasPublicationYear "2017" @default.
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