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Phagocytosing human polymorphonuclear leukocytes (hPMN) undergo accelerated apoptosis, a process referred to as phagocytosis-induced cell death (PICD) and an early step in their clearance from inflammatory sites. Among human pathogens that modulate hPMN apoptosis, Neisseria gonorrhoeae delays PICD, which may contribute to the exuberant neutrophilic inflammation that characterizes gonorrhea. To elucidate the mechanisms underlying delayed PICD, we compared features of hPMN cell death that followed phagocytosis of N. gonorrhoeae FA1090 wild-type (GC) or serum-opsonized zymosan (OPZ), a prototypical stimulus of PICD. Phosphatidylserine externalization required NADPH oxidase activity after ingestion of GC or OPZ, and annexin V staining and DNA fragmentation were less after phagocytosis of GC compared to OPZ. Caspase 3\/7 and caspase 9 activities after phagocytosis of GC were less than that seen after ingestion of OPZ, but caspase 8 activity was the same after ingestion of GC or OPZ. When hPMN sequentially ingested GC followed by OPZ, both caspase 3\/7 and 9 activities were less than that seen after OPZ alone, and the inhibition was dose dependent for GC, suggesting that ingestion of GC actively inhibited PICD. Sequential phagocytosis did not block caspase 8 activity, mitochondrial depolarization, or annexin V\/propidium iodide staining compared to responses of hPMN fed OPZ alone, despite inhibition of caspases 3\/7 and 9. Taken together, these data suggest that active inhibition of the intrinsic pathway of apoptosis contributes to the delay in PICD after hPMN ingestion of N. gonorrhoeae.<\/jats:p>","DOI":"10.1002\/jlb.4ma0820-649r","type":"journal-article","created":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T17:06:52Z","timestamp":1601053612000},"page":"1543-1553","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Modulation of phagocytosis-induced cell death of human neutrophils by\n                    <i>Neisseria gonorrhoeae<\/i>"],"prefix":"10.1093","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0855-1811","authenticated-orcid":true,"given":"Christine","family":"Cho","sequence":"first","affiliation":[{"name":"Inflammation Program and Department of Internal Medicine Roy J. and Lucille A Carver College of Medicine, University of Iowa and Veterans Administration Medical Center , Iowa City, Iowa , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athmane","family":"Teghanemt","sequence":"additional","affiliation":[{"name":"Inflammation Program and Department of Internal Medicine Roy J. and Lucille A Carver College of Medicine, University of Iowa and Veterans Administration Medical Center , Iowa City, Iowa , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A","family":"Apicella","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Roy J. and Lucille A. 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