title: Neisseria gonorrhoeae phagosomes delay fusion with primary granules to enhance bacterial survival inside human neutrophils.
abstract: Symptomatic infection with Neisseria gonorrhoeae (Gc) promotes inflammation driven by polymorphonuclear leucocytes (PMNs, neutrophils), yet some Gc survive PMN exposure during infection. Here we report a novel mechanism of gonococcal resistance to PMNs: Gc phagosomes avoid maturation into phagolysosomes by delayed fusion with primary (azurophilic) granules, which contain antimicrobial components including serine proteases. Reduced phagosome-primary granule fusion was observed in gonorrheal exudates and human PMNs infected ex vivo. Delayed phagosome-granule fusion could be overcome by opsonizing Gc with immunoglobulin. Using bacterial viability dyes along with antibodies to primary granules revealed that Gc survival in PMNs correlated with early residence in primary granule-negative phagosomes. However, when Gc was killed prior to PMN exposure, dead bacteria were also found in primary granule-negative phagosomes. These results suggest that Gc surface characteristics, rather than active bacterial processes, influence phagosome maturation and that Gc death inside PMNs occurs after phagosome-granule fusion. Ectopically increasing primary granule-phagosome fusion, by immunoglobulin opsonization or PMN treatment with lysophosphatidylcholine, reduced intracellular Gc viability, which was attributed in part to serine protease activity. We conclude that one method for Gc to avoid PMN clearance in acute gonorrhoea is by delaying primary granule-phagosome fusion, thus preventing formation of a degradative phagolysosome.
authors: Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, USA.
authors: M Brittany
authors: MB
authors: Johnson
authors: Alison K
authors: AK
authors: Criss
mesh_terms: D000818:Animals; D003594:Cytoplasmic Granules / Q000502:physiology*; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D016209:Interleukin-8 / Q000494:pharmacology; D008297:Male; D008561:Membrane Fusion / Q000502:physiology*; D050296:Microbial Viability / Q000187:drug effects; D009344:Neisseria gonorrhoeae / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology*; D009504:Neutrophils / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D010447:Peptide Hydrolases / Q000378:metabolism; D010588:Phagosomes / Q000382:microbiology / Q000502:physiology*; D057057:Serine Proteases / Q000378:metabolism
chemical_list: D007074:Immunoglobulin G; D016209:Interleukin-8; D010447:Peptide Hydrolases; D057057:Serine Proteases
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