Neisseria gonorrhoeae Elicits Extracellular Traps in Primary Neutrophil Culture While Suppressing the Oxidative Burst

ABSTRACT Neisseria gonorrhoeae (the gonococcus) causes gonorrhea and is uniquely adapted to survive within the human re-productive tract. Gonococci evade host immune surveillance in part by varying their pili and opacity-associated proteins. These variable surface antigens influence interactions with host epithelial and immune cells. A potent polymorphonuclear leukocyte (PMN) response is a hallmark of symptomatic gonococcal infection, with vast numbers of PMNs recruited to the site of infec-tion. A large body of literature describes gonococcus-PMN interactions, but the factors driving the outcome of infection are not fully understood. Gonococci have been described to both induce and suppress the PMN oxidative burst, but we determined that gonococci differentially affect induction of the PMN oxidative burst depending on the multiplicity of infection (MOI). Infecting PMN at anMOI of<20 gonococci elicits an oxidative burst, while anMOI of>20 suppresses the burst. Oxidative burst in re-sponse to gonococci is enhanced by, but does not require, expression of pili or opacity proteins. Neutrophil extracellular traps (NETs) were observed in gonococcus-infected PMNs, a process which requires an oxidative burst, yet gonococci induced NETs under suppressing conditions. The NETs were unable to kill gonococci despite killing the common vaginal bacterium Lactobacil-lus crispatus. Thus, gonococci influence PMN biology to promote their own survival by suppressing the oxidative burst of PMNs and stimulating the formation of NETs, which do not effectively kill gonococci, illustrating howN. gonorrhoeae has evolved to modulate PMN responses to promote infection. IMPORTANCE Neisseria gonorrhoeae, the gonococcus, is the only causative agent of gonorrhea and is exclusively found withi