title: Neisseria gonorrhoeae-mediated inhibition of apoptotic signalling in polymorphonuclear leukocytes.
abstract: The human pathogen Neisseria gonorrhoeae recruits and interacts extensively with polymorphonuclear leukocytes (PMNs) during infection. N. gonorrhoeae is able to survive the bactericidal activity of these innate immune cells and can actively modulate PMN functions in vitro. PMNs are short-lived cells which readily undergo apoptosis, and thus the effect of N. gonorrhoeae infection on PMN survival has implications for whether PMNs might serve as an important site of bacterial replication during infection. We developed and validated an HL-60 myeloid leukemia cell culture model for PMN infection and used both these cells and primary PMNs to show that N. gonorrhoeae infection alone does not induce apoptosis and furthermore that N. gonorrhoeae can inhibit both spontaneous apoptosis and apoptosis induced by the intrinsic and extrinsic apoptosis inducers staurosporine (STS) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), respectively. N. gonorrhoeae infection also results in the activation of NF-κB signaling in neutrophils and induces secretion of an identical profile of proinflammatory cytokines and chemokines in both HL-60 cells and primary PMNs. Our data show that the HL-60 cell line can be used to effectively model N. gonorrhoeae-PMN interactions and that N. gonorrhoeae actively inhibits apoptosis induced by multiple stimuli to prolong PMN survival and potentially facilitate bacterial survival, replication, and transmission.
authors.affiliation: Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, 303 E. Chicago Avenue, S213, Chicago, IL 60611, USA.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Chen
authors.forename: H Steven
authors.initials: HS
authors.lastname: Seifert
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000502:physiology; D018922:HL-60 Cells; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D009344:Neisseria gonorrhoeae / Q000502:physiology*; D009504:Neutrophils / Q000378:metabolism / Q000382:microbiology* / Q000502:physiology*; D021381:Protein Transport / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D019311:Staurosporine / Q000494:pharmacology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D016328:NF-kappa B; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D045304:Cytochromes c; D019311:Staurosporine